Variant 7-100826963-CCG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001363494.1(SLC12A9):c.-64_-63delGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,515,374 control chromosomes in the GnomAD database, including 965 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 258 hom., cov: 21)

Exomes 𝑓: 0.030 ( 707 hom. )

Consequence

SLC12A9
NM_001363494.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

EPHB4 (HGNC:3395): (EPH receptor B4) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]

EPHB4 links:

EPHB4 (HGNC:):

EPHB4 links:

SLC12A9 (HGNC:17435): (solute carrier family 12 member 9) Predicted to enable potassium:chloride symporter activity. Predicted to be involved in cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-100826963-CCG-C is Benign according to our data. Variant chr7-100826963-CCG-C is described in ClinVar as [Benign]. Clinvar id is 811647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100826963-CCG-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHB4	NM_004444.5 linkuse as main transcript	c.52+14_52+15delCG		intron_variant		ENST00000358173.8	NP_004435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHB4	ENST00000358173.8 linkuse as main transcript	c.52+14_52+15delCG		intron_variant		1	NM_004444.5	ENSP00000350896.3		P54760-1

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

6932

AN:

141158

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0171

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0396

AC:

6063

AN:

153260

Hom.:

193

AF XY:

0.0368

AC XY:

3026

AN XY:

82308

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0620

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.0407

Gnomad SAS exome

AF:

0.0378

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0283

GnomAD4 exome

AF:

0.0295

AC:

40552

AN:

1374096

Hom.:

707

AF XY:

0.0294

AC XY:

19952

AN XY:

679442

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0232

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0215

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0491

AC:

6941

AN:

141278

Hom.:

258

Cov.:

AF XY:

0.0479

AC XY:

3301

AN XY:

68984

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.0171

Gnomad4 EAS

AF:

0.0326

Gnomad4 SAS

AF:

0.0336

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0514

Asia WGS

AF:

0.0480

AC:

167

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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