chr7-107765469-C-T

Position:

• chr7-107765469-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.63

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 -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/exons	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.*386G>A		splice_region_variant	21/21	ENST00000340010.10	NP_000102.1
SLC26A3	NM_000111.3	c.*386G>A		3_prime_UTR_variant	21/21	ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.*386G>A		splice_region_variant	21/21	1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000340010	c.*386G>A		3_prime_UTR_variant	21/21	1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000379083.7	n.*2238G>A		splice_region_variant, non_coding_transcript_exon_variant	20/20	2		ENSP00000368375.3
SLC26A3	ENST00000379083.7	n.*2238G>A		3_prime_UTR_variant	20/20	2		ENSP00000368375.3

Frequencies

GnomAD3 genomes AF: 0.00673 AC: 1023 AN: 151986 Hom.: 18 Cov.: 31

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: 12 AN: 18902 Hom.: 3 Cov.: 0 AF XY: 0.000962 AC XY: 10 AN XY: 10392

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.: 18 Cov.: 31 AF XY: 0.00663 AC XY: 493 AN XY: 74348

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.: 0

Bravo AF: 0.00766

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital secretory diarrhea, chloride type Benign:1

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. -

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

Other links and lift over

dbSNP: rs183578733; hg19: chr7-107405914;