3-124284381-T-C

Position:

• chr3-124284381-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.970-14410T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,968 control chromosomes in the GnomAD database, including 30,317 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 0.63 (30317 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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 (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.970-14410T>C		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.970-14410T>C		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95502 AN: 151850 Hom.: 30292 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.629 AC: 95574 AN: 151968 Hom.: 30317 Cov.: 32 AF XY: 0.635 AC XY: 47137 AN XY: 74274

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.641

Alfa AF: 0.649 Hom.: 53797

Bravo AF: 0.617

Asia WGS AF: 0.792 AC: 2754 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	11
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2332769; hg19: chr3-124003228; COSMIC: COSV53757454;