rs7620580

Positions:

• chr3-124326456-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.1284+285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,096 control chromosomes in the GnomAD database, including 50,497 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 0.80 (50497 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.1284+285G>A		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.1284+285G>A		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122004 AN: 151978 Hom.: 50466 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.803 AC: 122086 AN: 152096 Hom.: 50497 Cov.: 32 AF XY: 0.805 AC XY: 59885 AN XY: 74356

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.809

Alfa AF: 0.865 Hom.: 11694

Bravo AF: 0.788

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7620580; hg19: chr3-124045303;