chr12-51486661-T-A

Variant names:

• chr12-51486661-T-A
• rs4761974
• NM_001039960.3:c.2286+761T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

SLC4A8 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039960.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	NM_001039960.3	MANE Select	c.2286+761T>A		intron	N/A	NP_001035049.1	Q2Y0W8-1
	SLC4A8	NM_001405270.1		c.2250+761T>A		intron	N/A	NP_001392199.1
	SLC4A8	NM_001258401.3		c.2127+761T>A		intron	N/A	NP_001245330.1	Q2Y0W8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.2286+761T>A		intron	N/A	ENSP00000405812.2	Q2Y0W8-1
	SLC4A8	ENST00000358657.7	TSL:1	c.2127+761T>A		intron	N/A	ENSP00000351483.4	Q2Y0W8-5
	SLC4A8	ENST00000877857.1		c.2286+761T>A		intron	N/A	ENSP00000547916.1

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

African (AFR) AF: 0.898 AC: 37285 AN: 41532

American (AMR) AF: 0.898 AC: 13730 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3386 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4749 AN: 5168

South Asian (SAS) AF: 0.898 AC: 4322 AN: 4812

European-Finnish (FIN) AF: 0.950 AC: 10068 AN: 10602

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64295 AN: 68024

Other (OTH) AF: 0.926 AC: 1960 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.46
PhyloP100		-0.93
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: rs4761974; hg19: chr12-51880445;