rs17683704

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000343.4(SLC5A1):c.1836A>G(p.Leu612Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,613,342 control chromosomes in the GnomAD database, including 3,936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 207 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3729 hom. )

Consequence

SLC5A1
NM_000343.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.03

Publications

8 publications found

Variant links:

Genes affected

SLC5A1 (HGNC:11036): (solute carrier family 5 member 1) This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SLC5A1 Gene-Disease associations (from GenCC):

glucose-galactose malabsorption
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC5A1 links:

LOC105373000 (HGNC:):

LOC105373000 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 22-32110054-A-G is Benign according to our data. Variant chr22-32110054-A-G is described in ClinVar as Benign. ClinVar VariationId is 341262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	NM_000343.4	MANE Select	c.1836A>G	p.Leu612Leu	synonymous	Exon 15 of 15	NP_000334.1
	SLC5A1	NM_001256314.2		c.1455A>G	p.Leu485Leu	synonymous	Exon 14 of 14	NP_001243243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.1836A>G	p.Leu612Leu	synonymous	Exon 15 of 15	ENSP00000266088.4
	SLC5A1	ENST00000543737.2	TSL:2	c.1455A>G	p.Leu485Leu	synonymous	Exon 14 of 14	ENSP00000444898.1

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6848

AN:

152178

Hom.:

208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0345

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.0556

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.0369

GnomAD2 exomes

AF:

0.0485

AC:

12187

AN:

251406

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0703

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0677

AC:

98865

AN:

1461046

Hom.:

3729

Cov.:

AF XY:

0.0669

AC XY:

48624

AN XY:

726886

show subpopulations

African (AFR)

AF:

0.00989

AC:

331

AN:

33472

American (AMR)

AF:

0.0318

AC:

1424

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1066

AN:

26134

East Asian (EAS)

AF:

0.00184

AC:

AN:

39700

South Asian (SAS)

AF:

0.0423

AC:

3652

AN:

86250

European-Finnish (FIN)

AF:

0.0565

AC:

3018

AN:

53418

Middle Eastern (MID)

AF:

0.0317

AC:

183

AN:

5768

European-Non Finnish (NFE)

AF:

0.0770

AC:

85617

AN:

1111216

Other (OTH)

AF:

0.0580

AC:

3501

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

4487

8973

13460

17946

22433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3144

6288

9432

12576

15720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0450

AC:

6849

AN:

152296

Hom.:

207

Cov.:

AF XY:

0.0435

AC XY:

3236

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0123

AC:

511

AN:

41562

American (AMR)

AF:

0.0348

AC:

532

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0377

AC:

182

AN:

4822

European-Finnish (FIN)

AF:

0.0556

AC:

590

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0705

AC:

4796

AN:

68022

Other (OTH)

AF:

0.0365

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

345

689

1034

1378

1723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0592

Hom.:

204

Bravo

AF:

0.0428

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0603

EpiControl

AF:

0.0659

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital glucose-galactose malabsorption

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.2

(source)

DANN

Benign

0.68

PhyloP100

1.0

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over