3-124093989-T-C

Position:

• chr3-124093989-T-C

Variant summary

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

The NM_001388419.1(KALRN):​c.73+60176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,892 control chromosomes in the GnomAD database, including 30,109 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 0.60 (30077 hom., cov: 31)
  • Exomes 𝑓: 0.75 (32 hom.)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.73+60176T>C		intron_variant		ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.73+60176T>C		intron_variant			NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90893 AN: 151666 Hom.: 30068 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.750 AC: 81 AN: 108 Hom.: 32 AF XY: 0.786 AC XY: 55 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.599 AC: 90920 AN: 151784 Hom.: 30077 Cov.: 31 AF XY: 0.597 AC XY: 44267 AN XY: 74180

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.622

Alfa AF: 0.722 Hom.: 48842

Bravo AF: 0.580

Asia WGS AF: 0.542 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10934657; hg19: chr3-123812836;