rs4730268

Variant names:

• chr7-107802941-C-T
• rs4730268
• NM_000111.3:c.-89+170G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000111.3(SLC26A3):​c.-89+170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,042 control chromosomes in the GnomAD database, including 2,865 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2865 hom., cov: 31)
• Consequence: SLC26A3 NM_000111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• congenital secretory chloride diarrhea 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.-89+170G>A		intron_variant	Intron 1 of 20	ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.-89+170G>A		intron_variant	Intron 1 of 20	1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000453332.1	c.-89+181G>A		intron_variant	Intron 1 of 3	4		ENSP00000395955.1
SLC26A3	ENST00000379083.7	n.-89+170G>A		intron_variant	Intron 1 of 19	2		ENSP00000368375.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27633 AN: 151924 Hom.: 2861 Cov.: 31

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27654 AN: 152042 Hom.: 2865 Cov.: 31 AF XY: 0.185 AC XY: 13746 AN XY: 74306

African (AFR) AF: 0.0897 AC: 3722 AN: 41494

American (AMR) AF: 0.245 AC: 3738 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3466

East Asian (EAS) AF: 0.146 AC: 757 AN: 5178

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2312 AN: 10522

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14836 AN: 67964

Other (OTH) AF: 0.202 AC: 426 AN: 2110

Alfa AF: 0.199 Hom.: 5145

Bravo AF: 0.177

Asia WGS AF: 0.212 AC: 736 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.30
PhyloP100		-0.77
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4730268; hg19: chr7-107443386;