Variant 3-124326012-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001388419.1(KALRN):c.1125C>T(p.Ser375=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,612,926 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 55 hom. )

Consequence

KALRN
NM_001388419.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.16

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-124326012-C-T is Benign according to our data. Variant chr3-124326012-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654085.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.16 with no splicing effect.

BS2

High AC in GnomAd4 at 1179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.1125C>T	p.Ser375=	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.1125C>T	p.Ser375=	synonymous_variant	7/60		NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1177

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00849

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00691

AC:

1721

AN:

249216

Hom.:

AF XY:

0.00686

AC XY:

925

AN XY:

134882

show subpopulations

Gnomad AFR exome

AF:

0.00625

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.00943

Gnomad SAS exome

AF:

0.00188

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00843

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.00801

AC:

11694

AN:

1460674

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

5706

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.00720

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.0211

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.00845

Gnomad4 OTH exome

AF:

0.00905

GnomAD4 genome

AF:

0.00774

AC:

1179

AN:

152252

Hom.:

Cov.:

AF XY:

0.00689

AC XY:

513

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00703

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00851

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00910

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00689

Hom.:

Bravo

AF:

0.00788

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00975

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

KALRN: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.60

DANN

Benign

0.74

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