3-124581410-C-T

Position:

• chr3-124581410-C-T

Variant summary

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

The NM_001388419.1(KALRN):​c.5182+18321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 141,652 control chromosomes in the GnomAD database, including 739 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 0.10 (739 hom., cov: 30)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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]

KALRN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.5182+18321C>T		intron_variant		ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.5182+18321C>T		intron_variant			NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 14257 AN: 141620 Hom.: 740 Cov.: 30

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.0644

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.101 AC: 14259 AN: 141652 Hom.: 739 Cov.: 30 AF XY: 0.0966 AC XY: 6628 AN XY: 68598

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.117

Alfa AF: 0.102 Hom.: 803

Bravo AF: 0.0968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2010099; hg19: chr3-124300257;