rs17286604

Variant names:

• chr3-124233370-C-T
• rs17286604
• NM_001388419.1:c.149-1459C>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.149-1459C>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 152,006 control chromosomes in the GnomAD database, including 7,587 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 (7587 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 6 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=-0.88).
• 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.149-1459C>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.149-1459C>T		intron_variant	Intron 2 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43069 AN: 151888 Hom.: 7587 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.283 AC: 43064 AN: 152006 Hom.: 7587 Cov.: 32 AF XY: 0.281 AC XY: 20846 AN XY: 74296

African (AFR) AF: 0.112 AC: 4653 AN: 41486

American (AMR) AF: 0.210 AC: 3208 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3470

East Asian (EAS) AF: 0.0186 AC: 96 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1581 AN: 4808

European-Finnish (FIN) AF: 0.398 AC: 4193 AN: 10542

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

European-Non Finnish (NFE) AF: 0.397 AC: 26938 AN: 67928

Other (OTH) AF: 0.274 AC: 577 AN: 2108

Alfa AF: 0.349 Hom.: 14546

Bravo AF: 0.258

Asia WGS AF: 0.162 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		-0.31
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: rs17286604; hg19: chr3-123952217;