Variant 3-124438959-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001388419.1(KALRN):c.3120G>A(p.Lys1040=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,614,080 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 31)

Exomes 𝑓: 0.014 ( 276 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.661

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 3-124438959-G-A is Benign according to our data. Variant chr3-124438959-G-A is described in ClinVar as [Benign]. Clinvar id is 3056205.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.661 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0696 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.3120G>A	p.Lys1040=	synonymous_variant	18/60	ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.3120G>A	p.Lys1040=	synonymous_variant	18/60		NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1829

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0759

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0152

AC:

3829

AN:

251216

Hom.:

AF XY:

0.0145

AC XY:

1964

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00992

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.0778

Gnomad SAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0142

AC:

20685

AN:

1461816

Hom.:

276

Cov.:

AF XY:

0.0140

AC XY:

10164

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.0828

Gnomad4 SAS exome

AF:

0.00619

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0120

AC:

1831

AN:

152264

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

929

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00258

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0757

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

EpiCase

AF:

0.0127

EpiControl

AF:

0.0114

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

Dec 27, 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

-0.46

CADD

Benign

4.3

DANN

Benign

0.61

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