rs11714061

Positions:

• chr3-124106675-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001388419.1(KALRN):​c.73+72862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,146 control chromosomes in the GnomAD database, including 1,612 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 0.13 (1612 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.73+72862G>A		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.73+72862G>A		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19486 AN: 152028 Hom.: 1608 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.128 AC: 19496 AN: 152146 Hom.: 1612 Cov.: 32 AF XY: 0.135 AC XY: 10057 AN XY: 74380

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.141

Alfa AF: 0.116 Hom.: 542

Bravo AF: 0.129

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.0
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11714061; hg19: chr3-123825522; COSMIC: COSV53757216;