rs13066449

Variant names:

• chr3-124232290-C-T
• rs13066449
• NM_001388419.1:c.149-2539C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.149-2539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,102 control chromosomes in the GnomAD database, including 7,590 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 0.28 (7590 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.149-2539C>T		intron_variant	Intron 2 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.149-2539C>T		intron_variant	Intron 2 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43070 AN: 151984 Hom.: 7590 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.283 AC: 43065 AN: 152102 Hom.: 7590 Cov.: 32 AF XY: 0.280 AC XY: 20840 AN XY: 74354

African (AFR) AF: 0.111 AC: 4626 AN: 41518

American (AMR) AF: 0.210 AC: 3205 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3468

East Asian (EAS) AF: 0.0186 AC: 96 AN: 5174

South Asian (SAS) AF: 0.328 AC: 1578 AN: 4814

European-Finnish (FIN) AF: 0.397 AC: 4199 AN: 10566

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26967 AN: 67954

Other (OTH) AF: 0.272 AC: 574 AN: 2108

Alfa AF: 0.346 Hom.: 1907

Bravo AF: 0.258

Asia WGS AF: 0.162 AC: 567 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.4
DANN	Benign	0.45
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13066449; hg19: chr3-123951137; COSMIC: COSV53761805;