Variant 3-124326102-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001388419.1(KALRN):c.1215C>T(p.Phe405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 1,613,528 control chromosomes in the GnomAD database, including 628,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 50198 hom., cov: 32)

Exomes 𝑓: 0.89 ( 578386 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.415

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 3-124326102-C-T is Benign according to our data. Variant chr3-124326102-C-T is described in ClinVar as [Benign]. Clinvar id is 1277522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.415 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 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.1215C>T	p.Phe405=	synonymous_variant	7/60	ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.1215C>T	p.Phe405=	synonymous_variant	7/60		NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121598

AN:

152018

Hom.:

50171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.581

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.842

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.906

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.807

GnomAD3 exomes

AF:

0.859

AC:

215370

AN:

250772

Hom.:

93498

AF XY:

0.867

AC XY:

117462

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.841

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.777

Gnomad SAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.906

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.864

GnomAD4 exome

AF:

0.888

AC:

1297320

AN:

1461392

Hom.:

578386

Cov.:

AF XY:

0.888

AC XY:

645651

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.572

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.837

Gnomad4 EAS exome

AF:

0.768

Gnomad4 SAS exome

AF:

0.884

Gnomad4 FIN exome

AF:

0.904

Gnomad4 NFE exome

AF:

0.905

Gnomad4 OTH exome

AF:

0.867

GnomAD4 genome

AF:

0.800

AC:

121674

AN:

152136

Hom.:

50198

Cov.:

AF XY:

0.802

AC XY:

59679

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.581

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.842

Gnomad4 EAS

AF:

0.776

Gnomad4 SAS

AF:

0.893

Gnomad4 FIN

AF:

0.906

Gnomad4 NFE

AF:

0.902

Gnomad4 OTH

AF:

0.807

Alfa

AF:

0.880

Hom.:

115536

Bravo

AF:

0.783

Asia WGS

AF:

0.827

AC:

2875

AN:

3478

EpiCase

AF:

0.898

EpiControl

AF:

0.894

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 27, 2021

- -

KALRN-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 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

-0.36

CADD

Benign

0.41

DANN

Benign

0.71

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