Variant rs78202770 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001388419.1(KALRN):c.5090C>A(p.Pro1697Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,367,892 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 Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 52 hom. )

Consequence

KALRN
NM_001388419.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.91

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:

KALRN (HGNC:):

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 (MetaRNN=0.005629152).

BP6

Variant 3-124562997-C-A is Benign according to our data. Variant chr3-124562997-C-A is described in ClinVar as [Benign]. Clinvar id is 3024845.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00672 (1024/152316) while in subpopulation EAS AF= 0.0484 (250/5170). AF 95% confidence interval is 0.0434. There are 14 homozygotes in gnomad4. There are 559 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1024 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.5090C>A	p.Pro1697Gln	missense_variant	34/60	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.5090C>A	p.Pro1697Gln	missense_variant	34/60		NM_001388419.1	ENSP00000508359.1		A0A804HLI0

Frequencies

GnomAD3 genomes

AF:

0.00671

AC:

1021

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0482

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00879

AC:

2187

AN:

248840

Hom.:

AF XY:

0.00908

AC XY:

1227

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.000780

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.0396

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.00942

GnomAD4 exome

AF:

0.00704

AC:

8557

AN:

1215576

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

4302

AN XY:

602448

show subpopulations

Gnomad4 AFR exome

AF:

0.000798

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.00266

Gnomad4 EAS exome

AF:

0.0430

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.00613

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.00672

AC:

1024

AN:

152316

Hom.:

Cov.:

AF XY:

0.00751

AC XY:

559

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0484

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00569

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00629

Hom.:

Bravo

AF:

0.00526

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00121

AC:

ESP6500EA

AF:

0.00583

AC:

ExAC

AF:

0.00836

AC:

1012

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

KALRN: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.78

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.30

Sift

Uncertain

0.0070

Sift4G

Benign

0.088

Vest4

0.72

MVP

0.80

ClinPred

0.017

GERP RS

4.5

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