rs1399650

Positions:

• chr2-161695208-G-A
• chr2-161695208-G-C

Variant summary

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

The NM_001178015.2(SLC4A10):​c.48+70642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,864 control chromosomes in the GnomAD database, including 48,906 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 0.80 (48906 hom., cov: 31)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A10	NM_001178015.2	c.48+70642G>A		intron_variant		ENST00000446997.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A10	ENST00000446997.6	c.48+70642G>A		intron_variant		1	NM_001178015.2	P4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121514 AN: 151746 Hom.: 48880 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.801 AC: 121585 AN: 151864 Hom.: 48906 Cov.: 31 AF XY: 0.799 AC XY: 59289 AN XY: 74218

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.806

Alfa AF: 0.835 Hom.: 103431

Bravo AF: 0.803

Asia WGS AF: 0.828 AC: 2860 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.72

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: rs1399650; hg19: chr2-162551718;