rs1373606

chr3-124295100-A-Cchr3-124295100-A-T

Variant summary

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

The NM_001388419.1(KALRN):c.970-3691A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,088 control chromosomes in the GnomAD database, including 21,829 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 0.53 (21829 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.970-3691A>C		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.970-3691A>C		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80336 AN: 151970 Hom.: 21816 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.529 AC: 80397 AN: 152088 Hom.: 21829 Cov.: 33 AF XY: 0.536 AC XY: 39872 AN XY: 74348

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.515

Alfa AF: 0.561 Hom.: 48310

Bravo AF: 0.513

Asia WGS AF: 0.656 AC: 2284 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	3.2
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1373606; hg19: chr3-124013947; COSMIC: COSV53757498;