chr12-51475314-G-A

Position:

• chr12-51475314-G-A

Variant summary

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

The NM_001039960.3(SLC4A8):​c.2172+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,040,646 control chromosomes in the GnomAD database, including 148,299 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 0.54 (22262 hom., cov: 32)
  • Exomes 𝑓: 0.53 (126037 hom.)
• Consequence: SLC4A8 NM_001039960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A8	NM_001039960.3	c.2172+108G>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.2172+108G>A		intron_variant		1	NM_001039960.3	ENSP00000405812.2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81964 AN: 151916 Hom.: 22253 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.529 AC: 470303 AN: 888612 Hom.: 126037 AF XY: 0.529 AC XY: 241506 AN XY: 456930

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.539 AC: 82022 AN: 152034 Hom.: 22262 Cov.: 32 AF XY: 0.539 AC XY: 40014 AN XY: 74298

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.524

Alfa AF: 0.536 Hom.: 3923

Bravo AF: 0.530

Asia WGS AF: 0.513 AC: 1786 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	0.60
DANN	Benign	0.31

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: rs868884; hg19: chr12-51869098; COSMIC: COSV60656867; COSMIC: COSV60656867;