rs2892769

Variant names:

• chr2-161733937-A-G
• rs2892769
• NM_001178015.2:c.49-37036A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-161733937-A-G
• chr2-161733937-A-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.49-37036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,938 control chromosomes in the GnomAD database, including 20,716 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 0.52 (20716 hom., cov: 31)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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.49-37036A>G		intron	N/A	NP_001171486.1
	SLC4A10	NM_001354440.2		c.49-37036A>G		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.84+23186A>G		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.49-37036A>G		intron	N/A	ENSP00000393066.1
	SLC4A10	ENST00000415876.6	TSL:1	c.49-37036A>G		intron	N/A	ENSP00000395797.2
	SLC4A10	ENST00000461456.5	TSL:1	n.285+25108A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78159 AN: 151820 Hom.: 20664 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.515 AC: 78273 AN: 151938 Hom.: 20716 Cov.: 31 AF XY: 0.518 AC XY: 38429 AN XY: 74238

African (AFR) AF: 0.637 AC: 26419 AN: 41466

American (AMR) AF: 0.546 AC: 8320 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2415 AN: 5144

South Asian (SAS) AF: 0.637 AC: 3068 AN: 4816

European-Finnish (FIN) AF: 0.417 AC: 4398 AN: 10548

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30252 AN: 67936

Other (OTH) AF: 0.520 AC: 1095 AN: 2106

Alfa AF: 0.465 Hom.: 22761

Bravo AF: 0.526

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-1.1
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: rs2892769; hg19: chr2-162590447;