Variant 3-124269192-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001388419.1(KALRN):c.906T>C(p.His302His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,610,832 control chromosomes in the GnomAD database, including 307,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.62 ( 29775 hom., cov: 33)

Exomes 𝑓: 0.62 ( 277995 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

KALRN links:

KALRN (HGNC:):

KALRN 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 (BayesDel_noAF=-0.63).

BP6

Variant 3-124269192-T-C is Benign according to our data. Variant chr3-124269192-T-C is described in ClinVar as [Benign]. Clinvar id is 3060559.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.906T>C	p.His302His	synonymous_variant	5/60	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.906T>C	p.His302His	synonymous_variant	5/60		NM_001388419.1	ENSP00000508359.1		A0A804HLI0

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94847

AN:

151984

Hom.:

29745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.658

GnomAD3 exomes

AF:

0.620

AC:

154702

AN:

249586

Hom.:

48207

AF XY:

0.617

AC XY:

83544

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.648

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.538

Gnomad SAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.612

Gnomad OTH exome

AF:

0.620

GnomAD4 exome

AF:

0.617

AC:

899517

AN:

1458730

Hom.:

277995

Cov.:

AF XY:

0.616

AC XY:

446472

AN XY:

725092

show subpopulations

Gnomad4 AFR exome

AF:

0.655

Gnomad4 AMR exome

AF:

0.684

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.624

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.624

AC:

94934

AN:

152102

Hom.:

29775

Cov.:

AF XY:

0.623

AC XY:

46317

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.660

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.614

Gnomad4 OTH

AF:

0.655

Alfa

AF:

0.616

Hom.:

55337

Bravo

AF:

0.632

Asia WGS

AF:

0.631

AC:

2195

AN:

3478

EpiCase

AF:

0.617

EpiControl

AF:

0.619

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KALRN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 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_noAF

Benign

-0.63

CADD

Benign

0.19

DANN

Benign

0.51

Splicing

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