12-51484976-G-A

Position:

• chr12-51484976-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001039960.3(SLC4A8):​c.2173-811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 152,250 control chromosomes in the GnomAD database, including 29 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 0.016 (29 hom., cov: 31)
• Consequence: SLC4A8 NM_001039960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2392/152250) while in subpopulation NFE AF= 0.0224 (1521/68014). AF 95% confidence interval is 0.0214. There are 29 homozygotes in gnomad4. There are 1139 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2392 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A8	NM_001039960.3	c.2173-811G>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.2173-811G>A		intron_variant		1	NM_001039960.3	ENSP00000405812.2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2396 AN: 152132 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0157 AC: 2392 AN: 152250 Hom.: 29 Cov.: 31 AF XY: 0.0153 AC XY: 1139 AN XY: 74452

Gnomad4 AFR AF: 0.00388

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0172 Hom.: 4

Bravo AF: 0.0139

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.79

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: rs147845115; hg19: chr12-51878760;