rs10497224

Variant names:

• chr2-161865863-T-A
• rs10497224
• NM_001178015.2:c.766+2801T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001178015.2(SLC4A10):​c.766+2801T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,766 control chromosomes in the GnomAD database, including 7,540 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 0.31 (7540 hom., cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	NM_001178015.2	MANE Select	c.766+2801T>A		intron	N/A	NP_001171486.1
	SLC4A10	NM_001354440.2		c.766+2801T>A		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.802+2801T>A		intron	N/A	NP_001341389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.766+2801T>A		intron	N/A	ENSP00000393066.1
	SLC4A10	ENST00000415876.6	TSL:1	c.766+2801T>A		intron	N/A	ENSP00000395797.2
	SLC4A10	ENST00000461456.5	TSL:1	n.1003+2801T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46758 AN: 151650 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.308 AC: 46807 AN: 151766 Hom.: 7540 Cov.: 32 AF XY: 0.308 AC XY: 22802 AN XY: 74130

African (AFR) AF: 0.283 AC: 11736 AN: 41448

American (AMR) AF: 0.395 AC: 6024 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1164 AN: 3464

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5180

South Asian (SAS) AF: 0.360 AC: 1739 AN: 4828

European-Finnish (FIN) AF: 0.283 AC: 2977 AN: 10528

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21980 AN: 67762

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.318 Hom.: 1024

Bravo AF: 0.315

Asia WGS AF: 0.209 AC: 722 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.31
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10497224; hg19: chr2-162722373;