Variant 3-124446759-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001388419.1(KALRN):c.3430-4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,614,068 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 56 hom. )

Consequence

KALRN
NM_001388419.1 splice_region, intron

Scores

Splicing: ADA: 0.0005052

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.394

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-124446759-A-T is Benign according to our data. Variant chr3-124446759-A-T is described in ClinVar as [Benign]. Clinvar id is 3037337.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.3430-4A>T		splice_region_variant, intron_variant		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.3430-4A>T		splice_region_variant, intron_variant			NM_001388419.1	ENSP00000508359.1		A0A804HLI0

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2290

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00382

AC:

960

AN:

251222

Hom.:

AF XY:

0.00278

AC XY:

378

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0527

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00152

AC:

2228

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

901

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.0151

AC:

2293

AN:

152268

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1060

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0512

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

May 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

-0.76

CADD

Benign

6.7

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00051

dbscSNV1_RF

Benign

0.014

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