rs17683704

Variant names:

• chr22-32110054-A-G
• rs17683704
• NM_000343.4:c.1836A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.03
• Publications: 8 publications found

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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

LOC105373000 (HGNC:):

ACMG classification

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

Sel.	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	P13866-1
	SLC5A1	NM_001256314.2		c.1455A>G	p.Leu485Leu	synonymous	Exon 14 of 14	NP_001243243.1	P13866-2

Ensembl Transcripts

Sel.	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	P13866-1
	SLC5A1	ENST00000878506.1		c.1728A>G	p.Leu576Leu	synonymous	Exon 14 of 14	ENSP00000548565.1
	SLC5A1	ENST00000543737.2	TSL:2	c.1455A>G	p.Leu485Leu	synonymous	Exon 14 of 14	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6848 AN: 152178 Hom.: 208 Cov.: 32

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

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.: 32 AF XY: 0.0669 AC XY: 48624 AN XY: 726886

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: 73 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

GnomAD4 genome AF: 0.0450 AC: 6849 AN: 152296 Hom.: 207 Cov.: 32 AF XY: 0.0435 AC XY: 3236 AN XY: 74476

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: 6 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: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4796 AN: 68022

Other (OTH) AF: 0.0365 AC: 77 AN: 2110

Alfa AF: 0.0592 Hom.: 204

Bravo AF: 0.0428

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0603

EpiControl AF: 0.0659

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital glucose-galactose malabsorption (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.2
DANN	Benign	0.68
PhyloP100		1.0
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17683704; hg19: chr22-32506041; COSMIC: COSV56683005;