Variant 12-49544303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_012284.3(KCNH3):c.1110C>T(p.Leu370Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,613,056 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 3 hom. )

Consequence

KCNH3
NM_012284.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.741

Variant links:

Genes affected

KCNH3 (HGNC:6252): (potassium voltage-gated channel subfamily H member 3) The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

KCNH3 links:

KCNH3 (HGNC:):

KCNH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-49544303-C-T is Benign according to our data. Variant chr12-49544303-C-T is described in ClinVar as [Benign]. Clinvar id is 713125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.741 with no splicing effect.

BS2

High AC in GnomAd4 at 503 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH3	NM_012284.3 linkuse as main transcript	c.1110C>T	p.Leu370Leu	synonymous_variant	7/15	ENST00000257981.7	NP_036416.1	Q9ULD8
KCNH3	NM_001314030.2 linkuse as main transcript	c.930C>T	p.Leu310Leu	synonymous_variant	7/15		NP_001300959.1	Q9ULD8
KCNH3	XM_011538085.3 linkuse as main transcript	c.1110C>T	p.Leu370Leu	synonymous_variant	7/15		XP_011536387.1
KCNH3	XM_047428613.1 linkuse as main transcript	c.1110C>T	p.Leu370Leu	synonymous_variant	7/10		XP_047284569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNH3	ENST00000257981.7 linkuse as main transcript	c.1110C>T	p.Leu370Leu	synonymous_variant	7/15	1	NM_012284.3	ENSP00000257981.5	Q9ULD8
KCNH3	ENST00000551415.1 linkuse as main transcript	n.50C>T		non_coding_transcript_exon_variant	1/2	3
KCNH3	ENST00000649994.1 linkuse as main transcript	n.*720C>T		non_coding_transcript_exon_variant	8/16			ENSP00000497890.1	A0A3B3ITH0
KCNH3	ENST00000649994.1 linkuse as main transcript	n.*720C>T		3_prime_UTR_variant	8/16			ENSP00000497890.1	A0A3B3ITH0

Frequencies

GnomAD3 genomes

AF:

0.00330

AC:

503

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000825

AC:

206

AN:

249646

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000437

AC:

638

AN:

1460700

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

280

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000572

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00330

AC:

503

AN:

152356

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

252

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00372

Asia WGS

AF:

0.000289

AC:

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

DANN

Benign

0.93

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