Variant 3-124329917-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001388419.1(KALRN):c.1341C>T(p.Ser447=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,613,416 control chromosomes in the GnomAD database, including 6,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 908 hom., cov: 31)

Exomes 𝑓: 0.084 ( 5682 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.44

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 3-124329917-C-T is Benign according to our data. Variant chr3-124329917-C-T is described in ClinVar as [Benign]. Clinvar id is 3057229.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.1341C>T	p.Ser447=	synonymous_variant	8/60	ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.1341C>T	p.Ser447=	synonymous_variant	8/60		NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15576

AN:

151734

Hom.:

908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.0873

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.0961

AC:

24140

AN:

251236

Hom.:

1321

AF XY:

0.0944

AC XY:

12813

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.0928

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0760

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0842

AC:

123068

AN:

1461564

Hom.:

5682

Cov.:

AF XY:

0.0846

AC XY:

61533

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.149

Gnomad4 SAS exome

AF:

0.0937

Gnomad4 FIN exome

AF:

0.0725

Gnomad4 NFE exome

AF:

0.0772

Gnomad4 OTH exome

AF:

0.0921

GnomAD4 genome

AF:

0.103

AC:

15584

AN:

151852

Hom.:

908

Cov.:

AF XY:

0.102

AC XY:

7537

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.0864

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0762

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0885

Hom.:

832

Bravo

AF:

0.108

Asia WGS

AF:

0.111

AC:

386

AN:

3478

EpiCase

AF:

0.0829

EpiControl

AF:

0.0868

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KALRN-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 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

-0.70

CADD

Benign

1.0

DANN

Benign

0.54

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