rs17683704

chr22-32110054-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000343.4(SLC5A1):c.1836A>G(p.Leu612=) 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:3
• Conservation: PhyloP100: 1.03

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]

LOC105373000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A1	NM_000343.4	c.1836A>G	p.Leu612=	synonymous_variant	15/15	ENST00000266088.9
LOC105373000	XR_938172.3	n.408-3112T>C		intron_variant, non_coding_transcript_variant
SLC5A1	NM_001256314.2	c.1455A>G	p.Leu485=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A1	ENST00000266088.9	c.1836A>G	p.Leu612=	synonymous_variant	15/15	1	NM_000343.4	P1
SLC5A1	ENST00000543737.2	c.1455A>G	p.Leu485=	synonymous_variant	14/14	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

GnomAD3 exomes AF: 0.0485 AC: 12187 AN: 251406 Hom.: 371 AF XY: 0.0495 AC XY: 6721 AN XY: 135868

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 SAS exome AF: 0.0390

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

Gnomad4 AFR exome AF: 0.00989

Gnomad4 AMR exome AF: 0.0318

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.00184

Gnomad4 SAS exome AF: 0.0423

Gnomad4 FIN exome AF: 0.0565

Gnomad4 NFE exome AF: 0.0770

Gnomad4 OTH exome AF: 0.0580

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

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0556

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0602 Hom.: 187

Bravo AF: 0.0428

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0603

EpiControl AF: 0.0659

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital glucose-galactose malabsorption Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	2.2
Dann	Benign	0.68

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

LitVar

Other links and lift over

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