rs73419912

chr7-107791855-G-Achr7-107791855-G-Cchr7-107791855-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000111.3(SLC26A3):c.357C>T(p.Phe119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,612,592 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (5 hom.)
• Consequence: SLC26A3 NM_000111.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.455

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 7-107791855-G-A is Benign according to our data. Variant chr7-107791855-G-A is described in ClinVar as [Benign]. Clinvar id is 776252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107791855-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00437 (665/152188) while in subpopulation AFR AF= 0.0133 (553/41536). AF 95% confidence interval is 0.0124. There are 4 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A3	NM_000111.3	c.357C>T	p.Phe119=	synonymous_variant	4/21	ENST00000340010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A3	ENST00000340010.10	c.357C>T	p.Phe119=	synonymous_variant	4/21	1	NM_000111.3	P1
SLC26A3	ENST00000453332.1	c.357C>T	p.Phe119=	synonymous_variant	4/4	4
SLC26A3	ENST00000379083.7	c.*148C>T		3_prime_UTR_variant, NMD_transcript_variant	4/20	2

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152070 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00171 AC: 431 AN: 251348 Hom.: 2 AF XY: 0.00148 AC XY: 201 AN XY: 135834

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00148 AC: 2157 AN: 1460404 Hom.: 5 Cov.: 29 AF XY: 0.00138 AC XY: 1005 AN XY: 726596

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00437 AC: 665 AN: 152188 Hom.: 4 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74410

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00975 Hom.: 18

Bravo AF: 0.00488

EpiCase AF: 0.000818

EpiControl AF: 0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	SLC26A3: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Congenital secretory diarrhea, chloride type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.8
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.35		Position offset: -25

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

Publications

LitVar

Other links and lift over

dbSNP: rs73419912; hg19: chr7-107432300; COSMIC: COSV104641910; COSMIC: COSV104641910;