rs1493193

Positions:

• chr12-51512565-C-A
• chr12-51512565-C-G

Variant summary

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

The NM_001039960.3(SLC4A8):​c.*5127C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,402 control chromosomes in the GnomAD database, including 65,411 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 (65335 hom., cov: 31)
  • Exomes 𝑓: 0.95 (76 hom.)
• Consequence: SLC4A8 NM_001039960.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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=-0.81).
• 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.*5127C>A		3_prime_UTR_variant	25/25	ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7	c.*5127C>A		3_prime_UTR_variant	25/25	1	NM_001039960.3	ENSP00000405812.2
SLC4A8	ENST00000358657.7	c.*5127C>A		3_prime_UTR_variant	25/25	1		ENSP00000351483.4

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140862 AN: 152118 Hom.: 65285 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.926

GnomAD4 exome AF: 0.952 AC: 158 AN: 166 Hom.: 76 Cov.: 0 AF XY: 0.935 AC XY: 101 AN XY: 108

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.944

Gnomad4 OTH exome AF: 0.938

GnomAD4 genome AF: 0.926 AC: 140969 AN: 152236 Hom.: 65335 Cov.: 31 AF XY: 0.925 AC XY: 68833 AN XY: 74434

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.926

Alfa AF: 0.933 Hom.: 11721

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	-0.81
CADD	Benign	2.2
DANN	Benign	0.69

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: rs1493193; hg19: chr12-51906349;