Variant rs2279784 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388419.1(KALRN):c.4936-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,175,368 control chromosomes in the GnomAD database, including 12,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2493 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9786 hom. )

Consequence

KALRN
NM_001388419.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.551

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:

LOC105374076 (HGNC:):

LOC105374076 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 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.4936-86G>A		intron_variant		ENST00000682506.1
LOC105374076	XR_001740872.2 linkuse as main transcript	n.187-7536C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.4936-86G>A		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21628

AN:

150336

Hom.:

2481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.112

AC:

114698

AN:

1024914

Hom.:

9786

Cov.:

AF XY:

0.115

AC XY:

56796

AN XY:

495470

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.0882

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.144

AC:

21667

AN:

150454

Hom.:

2493

Cov.:

AF XY:

0.155

AC XY:

11383

AN XY:

73334

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.0930

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.107

Hom.:

1396

Bravo

AF:

0.155

Asia WGS

AF:

0.387

AC:

1342

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.63

DANN

Benign

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over