Variant chr4-103031712-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_178833.7(SLC9B2):c.1243C>G(p.Pro415Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,611,908 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 40 hom. )

Consequence

SLC9B2
NM_178833.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

SLC9B2 (HGNC:25143): (solute carrier family 9 member B2) Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]

SLC9B2 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=0.0028415918).

BP6

Variant 4-103031712-G-C is Benign according to our data. Variant chr4-103031712-G-C is described in ClinVar as [Benign]. Clinvar id is 775219.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1596/152178) while in subpopulation AFR AF= 0.0327 (1356/41522). AF 95% confidence interval is 0.0312. There are 19 homozygotes in gnomad4. There are 739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9B2	NM_178833.7 linkuse as main transcript	c.1243C>G	p.Pro415Ala	missense_variant	10/12	ENST00000394785.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9B2	ENST00000394785.9 linkuse as main transcript	c.1243C>G	p.Pro415Ala	missense_variant	10/12	2	NM_178833.7	P1	Q86UD5-1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1589

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00525

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00369

AC:

924

AN:

250410

Hom.:

AF XY:

0.00306

AC XY:

414

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.000996

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00207

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00219

AC:

3202

AN:

1459730

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1565

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.0324

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.0105

AC:

1596

AN:

152178

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

739

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.00524

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00414

AC:

503

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.066

T;.;T;T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L;.;.

MutationTaster

Benign

0.95

D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.44

T;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.014

B;.;B;B;B

Vest4

0.40

MVP

0.37

MPC

0.020

ClinPred

0.020

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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