22-32086334-T-G

Position:

chr22-32086334-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000266088.9(SLC5A1):c.1129+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,588,556 control chromosomes in the GnomAD database, including 131,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20763 hom., cov: 31)

Exomes 𝑓: 0.38 ( 110970 hom. )

Consequence

SLC5A1
ENST00000266088.9 splice_region, intron

Scores

Splicing: ADA: 0.00002167

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.979

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-32086334-T-G is Benign according to our data. Variant chr22-32086334-T-G is described in ClinVar as [Benign]. Clinvar id is 341249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-32086334-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SLC5A1	NM_000343.4 linkuse as main transcript	c.1129+7T>G	splice_region_variant, intron_variant	ENST00000266088.9	NP_000334.1
SLC5A1	NM_001256314.2 linkuse as main transcript	c.748+7T>G	splice_region_variant, intron_variant		NP_001243243.1
SLC5A1	XM_011530331.2 linkuse as main transcript	c.1129+7T>G	splice_region_variant, intron_variant		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9 linkuse as main transcript	c.1129+7T>G	splice_region_variant, intron_variant	1	NM_000343.4	ENSP00000266088	P1	P13866-1
SLC5A1	ENST00000543737.2 linkuse as main transcript	c.748+7T>G	splice_region_variant, intron_variant	2		ENSP00000444898		P13866-2
SLC5A1	ENST00000477969.1 linkuse as main transcript	n.295+7T>G	splice_region_variant, intron_variant, non_coding_transcript_variant	3
SLC5A1	ENST00000486394.1 linkuse as main transcript		downstream_gene_variant	4

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72305

AN:

151838

Hom.:

20709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.425

GnomAD3 exomes

AF:

0.362

AC:

90985

AN:

251372

Hom.:

18977

AF XY:

0.359

AC XY:

48756

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.827

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.382

AC:

548795

AN:

1436600

Hom.:

110970

Cov.:

AF XY:

0.380

AC XY:

272334

AN XY:

716406

show subpopulations

Gnomad4 AFR exome

AF:

0.839

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.477

AC:

72421

AN:

151956

Hom.:

20763

Cov.:

AF XY:

0.466

AC XY:

34580

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.815

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.278

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.415

Hom.:

6730

Bravo

AF:

0.494

Asia WGS

AF:

0.327

AC:

1137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital glucose-galactose malabsorption

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.84

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over