rs2084543

chr2-161839904-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001178015.2(SLC4A10):c.393C>T(p.Asp131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,613,532 control chromosomes in the GnomAD database, including 4,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (368 hom., cov: 32)
  • Exomes 𝑓: 0.072 (4235 hom.)
• Consequence: SLC4A10 NM_001178015.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.322

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-161839904-C-T is Benign according to our data. Variant chr2-161839904-C-T is described in ClinVar as [Benign]. Clinvar id is 586611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.322 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A10	NM_001178015.2	c.393C>T	p.Asp131=	synonymous_variant	4/27	ENST00000446997.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A10	ENST00000446997.6	c.393C>T	p.Asp131=	synonymous_variant	4/27	1	NM_001178015.2	P4

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9230 AN: 151984 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.0699

GnomAD3 exomes AF: 0.0736 AC: 18345 AN: 249270 Hom.: 831 AF XY: 0.0758 AC XY: 10252 AN XY: 135228

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.0790

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0755

Gnomad OTH exome AF: 0.0762

GnomAD4 exome AF: 0.0724 AC: 105851 AN: 1461430 Hom.: 4235 Cov.: 31 AF XY: 0.0735 AC XY: 53468 AN XY: 727010

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.0482

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0790

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0725

Gnomad4 OTH exome AF: 0.0666

GnomAD4 genome AF: 0.0607 AC: 9234 AN: 152102 Hom.: 368 Cov.: 32 AF XY: 0.0637 AC XY: 4735 AN XY: 74344

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0868

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0729

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0700 Hom.: 664

Bravo AF: 0.0550

Asia WGS AF: 0.101 AC: 352 AN: 3478

EpiCase AF: 0.0747

EpiControl AF: 0.0786

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	13
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2084543; hg19: chr2-162696414; COSMIC: COSV55792824; COSMIC: COSV55792824;