rs4500960

Variant names:

• chr2-161962111-C-T
• rs4500960
• NM_001178015.2:c.2863-2024C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

SLC4A10 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178015.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	NM_001178015.2	MANE Select	c.2863-2024C>T		intron	N/A	NP_001171486.1
	SLC4A10	NM_001354440.2		c.2863-2024C>T		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.2899-2024C>T		intron	N/A	NP_001341389.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.2863-2024C>T		intron	N/A	ENSP00000393066.1
	SLC4A10	ENST00000415876.6	TSL:1	c.2773-2024C>T		intron	N/A	ENSP00000395797.2
	SLC4A10	ENST00000272716.9	TSL:5	c.2773-2024C>T		intron	N/A	ENSP00000272716.5

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

African (AFR) AF: 0.524 AC: 21700 AN: 41448

American (AMR) AF: 0.498 AC: 7602 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1847 AN: 5182

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3970 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31344 AN: 67922

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.476 Hom.: 8899

Bravo AF: 0.482

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.49
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4500960; hg19: chr2-162818621;