rs4730268

Positions:

• chr7-107802941-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
SLC26A3	NM_000111.3	c.-89+170G>A		intron_variant		ENST00000340010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A3	ENST00000340010.10	c.-89+170G>A		intron_variant		1	NM_000111.3	P1
SLC26A3	ENST00000453332.1	c.-89+181G>A		intron_variant		4
SLC26A3	ENST00000379083.7	c.-89+170G>A		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.202

Alfa AF: 0.213 Hom.: 504

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4730268; hg19: chr7-107443386;