rs17221479

Positions:

• chr3-124258631-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.264-5867G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,188 control chromosomes in the GnomAD database, including 508 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 0.078 (508 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.264-5867G>A		intron_variant		ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.264-5867G>A		intron_variant			NM_001388419.1	ENSP00000508359	A2

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11823 AN: 152070 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.0871

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

GnomAD4 genome AF: 0.0777 AC: 11822 AN: 152188 Hom.: 508 Cov.: 32 AF XY: 0.0790 AC XY: 5880 AN XY: 74396

Gnomad4 AFR AF: 0.0621

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0845 Hom.: 73

Bravo AF: 0.0724

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17221479; hg19: chr3-123977478; COSMIC: COSV53757376;