rs4761974

Positions:

• chr12-51486661-T-A
• chr12-51486661-T-C
• chr12-51486661-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039960.3(SLC4A8):​c.2286+761T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,222 control chromosomes in the GnomAD database, including 65,332 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 0.93 (65332 hom., cov: 31)
• Consequence: SLC4A8 NM_001039960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

Genes affected

SLC4A8 (HGNC:11034): (solute carrier family 4 member 8) The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A8	NM_001039960.3	c.2286+761T>A		intron_variant		ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7	c.2286+761T>A		intron_variant		1	NM_001039960.3	ENSP00000405812	P1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140852 AN: 152104 Hom.: 65281 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.926

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

GnomAD4 genome AF: 0.926 AC: 140960 AN: 152222 Hom.: 65332 Cov.: 31 AF XY: 0.925 AC XY: 68824 AN XY: 74426

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.898

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.926

Alfa AF: 0.938 Hom.: 8316

Bravo AF: 0.921

Asia WGS AF: 0.899 AC: 3128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.46

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: rs4761974; hg19: chr12-51880445;