rs4500960

Positions:

• chr2-161962111-C-T

Variant summary

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

The NM_001178015.2(SLC4A10):​c.2863-2024C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,970 control chromosomes in the GnomAD database, including 17,440 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 0.48 (17440 hom., cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A10	NM_001178015.2	c.2863-2024C>T		intron_variant		ENST00000446997.6	NP_001171486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6	c.2863-2024C>T		intron_variant		1	NM_001178015.2	ENSP00000393066.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72330 AN: 151852 Hom.: 17405 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.477 AC: 72433 AN: 151970 Hom.: 17440 Cov.: 32 AF XY: 0.477 AC XY: 35446 AN XY: 74278

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.477

Alfa AF: 0.477 Hom.: 7981

Bravo AF: 0.482

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.49

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: rs4500960; hg19: chr2-162818621;