Variant 21-37840718-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000609713.2(KCNJ6):c.-27-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,507,856 control chromosomes in the GnomAD database, including 247,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.59 ( 26473 hom., cov: 33)

Exomes 𝑓: 0.57 ( 221026 hom. )

Consequence

KCNJ6
ENST00000609713.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002224

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.906

Variant links:

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

KCNJ6 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 21-37840718-G-A is Benign according to our data. Variant chr21-37840718-G-A is described in ClinVar as [Benign]. Clinvar id is 1226048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5 linkuse as main transcript	c.-27-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000609713.2	NP_002231.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
KCNJ6	ENST00000609713.2 linkuse as main transcript	c.-27-9C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_002240.5	ENSP00000477437	P1
KCNJ6	ENST00000645093.1 linkuse as main transcript	c.-27-9C>T	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000493772	P1
	ENST00000692486.2 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89359

AN:

151958

Hom.:

26464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.608

GnomAD3 exomes

AF:

0.591

AC:

142673

AN:

241300

Hom.:

42910

AF XY:

0.590

AC XY:

77388

AN XY:

131122

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.594

Gnomad ASJ exome

AF:

0.671

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.606

Gnomad FIN exome

AF:

0.524

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.567

AC:

769313

AN:

1355780

Hom.:

221026

Cov.:

AF XY:

0.569

AC XY:

386834

AN XY:

680092

show subpopulations

Gnomad4 AFR exome

AF:

0.607

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.607

Gnomad4 FIN exome

AF:

0.526

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.588

AC:

89411

AN:

152076

Hom.:

26473

Cov.:

AF XY:

0.588

AC XY:

43697

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.610

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.780

Gnomad4 SAS

AF:

0.624

Gnomad4 FIN

AF:

0.528

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.578

Hom.:

5635

Bravo

AF:

0.597

Asia WGS

AF:

0.674

AC:

2345

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.60

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0040

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