chr7-107765469-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000111.3(SLC26A3):c.*386G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 171,006 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 18 hom., cov: 31)

Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

SLC26A3
NM_000111.3 splice_region

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.63

Variant links:

Genes affected

SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

SLC26A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-107765469-C-T is Benign according to our data. Variant chr7-107765469-C-T is described in ClinVar as [Benign]. Clinvar id is 358530.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00672 (1022/152104) while in subpopulation AFR AF= 0.0238 (989/41506). AF 95% confidence interval is 0.0226. There are 18 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A3	NM_000111.3 link	c.*386G>A		splice_region_variant	Exon 21 of 21	ENST00000340010.10	NP_000102.1	P40879
SLC26A3	NM_000111.3 link	c.*386G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000340010.10	NP_000102.1	P40879

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A3	ENST00000340010.10 link	c.*386G>A	splice_region_variant	Exon 21 of 21	1	NM_000111.3	ENSP00000345873.5	P40879
SLC26A3	ENST00000340010 link	c.*386G>A	3_prime_UTR_variant	Exon 21 of 21	1	NM_000111.3	ENSP00000345873.5	P40879
SLC26A3	ENST00000379083.7 link	n.*2238G>A	splice_region_variant, non_coding_transcript_exon_variant	Exon 20 of 20	2		ENSP00000368375.3	F8WBL6
SLC26A3	ENST00000379083.7 link	n.*2238G>A	3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000368375.3	F8WBL6

Frequencies

GnomAD3 genomes

AF:

0.00673

AC:

1023

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00385

GnomAD4 exome

AF:

0.000635

AC:

AN:

18902

Hom.:

Cov.:

AF XY:

0.000962

AC XY:

AN XY:

10392

show subpopulations

Gnomad4 AFR exome

AF:

0.0294

Gnomad4 AMR exome

AF:

0.000512

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000923

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000858

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00672

AC:

1022

AN:

152104

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

493

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00766

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital secretory diarrhea, chloride type

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.82

DANN

Benign

0.63

Splicing

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