Variant 3-124228048-G-A 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.132G>A(p.Lys44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,613,456 control chromosomes in the GnomAD database, including 4,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.099 ( 1132 hom., cov: 31)

Exomes 𝑓: 0.056 ( 3765 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.01

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:

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=-0.47).

BP6

Variant 3-124228048-G-A is Benign according to our data. Variant chr3-124228048-G-A is described in ClinVar as [Benign]. Clinvar id is 3060740.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 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.132G>A	p.Lys44=	synonymous_variant	2/60	ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.132G>A	p.Lys44=	synonymous_variant	2/60		NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0989

AC:

15037

AN:

152036

Hom.:

1129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0564

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0800

GnomAD3 exomes

AF:

0.0896

AC:

22534

AN:

251414

Hom.:

1490

AF XY:

0.0831

AC XY:

11294

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.0590

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0526

Gnomad NFE exome

AF:

0.0389

Gnomad OTH exome

AF:

0.0779

GnomAD4 exome

AF:

0.0563

AC:

82344

AN:

1461302

Hom.:

3765

Cov.:

AF XY:

0.0564

AC XY:

41010

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0594

Gnomad4 EAS exome

AF:

0.186

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0541

Gnomad4 NFE exome

AF:

0.0380

Gnomad4 OTH exome

AF:

0.0724

GnomAD4 genome

AF:

0.0990

AC:

15069

AN:

152154

Hom.:

1132

Cov.:

AF XY:

0.101

AC XY:

7514

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.0564

Gnomad4 NFE

AF:

0.0382

Gnomad4 OTH

AF:

0.0801

Alfa

AF:

0.0679

Hom.:

410

Bravo

AF:

0.109

Asia WGS

AF:

0.176

AC:

610

AN:

3478

EpiCase

AF:

0.0421

EpiControl

AF:

0.0412

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

Nov 18, 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

-0.47

CADD

Benign

DANN

Benign

0.62

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