rs1979112

Variant names:

• chr2-161801445-A-C
• rs1979112
• NM_001178015.2:c.131-3004A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-161801445-A-C
• chr2-161801445-A-G

Variant summary

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

The NM_001178015.2(SLC4A10):​c.131-3004A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,834 control chromosomes in the GnomAD database, including 7,625 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 0.26 (7625 hom., cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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.131-3004A>C		intron	N/A	NP_001171486.1
	SLC4A10	NM_001354440.2		c.131-3004A>C		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.167-3004A>C		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.131-3004A>C		intron	N/A	ENSP00000393066.1
	SLC4A10	ENST00000415876.6	TSL:1	c.131-3004A>C		intron	N/A	ENSP00000395797.2
	SLC4A10	ENST00000461456.5	TSL:1	n.368-3004A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39526 AN: 151716 Hom.: 7583 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.261 AC: 39625 AN: 151834 Hom.: 7625 Cov.: 32 AF XY: 0.259 AC XY: 19259 AN XY: 74216

African (AFR) AF: 0.551 AC: 22825 AN: 41420

American (AMR) AF: 0.179 AC: 2726 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3466

East Asian (EAS) AF: 0.155 AC: 800 AN: 5156

South Asian (SAS) AF: 0.166 AC: 801 AN: 4812

European-Finnish (FIN) AF: 0.185 AC: 1959 AN: 10562

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9310 AN: 67896

Other (OTH) AF: 0.239 AC: 503 AN: 2108

Alfa AF: 0.134 Hom.: 917

Bravo AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.33
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: rs1979112; hg19: chr2-162657955;