Variant 2-161708815-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001178015.2(SLC4A10):c.49-62158T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,532,466 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 74 hom. )

Consequence

SLC4A10
NM_001178015.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021554232).

BP6

Variant 2-161708815-T-G is Benign according to our data. Variant chr2-161708815-T-G is described in ClinVar as [Benign]. Clinvar id is 3038020.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A10	NM_001178015.2 linkuse as main transcript	c.49-62158T>G		intron_variant		ENST00000446997.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A10	ENST00000446997.6 linkuse as main transcript	c.49-62158T>G		intron_variant		1	NM_001178015.2	P4	Q6U841-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2800

AN:

151538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00261

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000310

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.00340

AC:

454

AN:

133368

Hom.:

AF XY:

0.00257

AC XY:

187

AN XY:

72682

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00188

AC:

2597

AN:

1380810

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1161

AN XY:

681346

show subpopulations

Gnomad4 AFR exome

AF:

0.0656

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00240

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000177

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000919

Gnomad4 OTH exome

AF:

0.00418

GnomAD4 genome

AF:

0.0185

AC:

2806

AN:

151656

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1306

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.0634

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.00261

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000310

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.0209

ExAC

AF:

0.00214

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC4A10-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.088

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N

PROVEAN

Benign

0.25

REVEL

Benign

0.25

Sift

Benign

0.36

Sift4G

Benign

0.54

Vest4

0.26

MVP

0.37

ClinPred

0.020

GERP RS

4.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over