3-124049075-T-G

Position:

• chr3-124049075-T-G

Variant summary

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

The NM_001388419.1(KALRN):​c.73+15262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,122 control chromosomes in the GnomAD database, including 42,641 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 0.74 (42641 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.73+15262T>G		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+15262T>G		intron_variant			NM_001388419.1	ENSP00000508359.1
KALRN	ENST00000683571.1	c.73+15262T>G		intron_variant				ENSP00000506888.1
KALRN	ENST00000682861.1	c.73+15262T>G		intron_variant				ENSP00000506756.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112441 AN: 152002 Hom.: 42619 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.740 AC: 112505 AN: 152122 Hom.: 42641 Cov.: 32 AF XY: 0.736 AC XY: 54765 AN XY: 74370

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.732

Alfa AF: 0.815 Hom.: 86003

Bravo AF: 0.727

Asia WGS AF: 0.609 AC: 2121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2332690; hg19: chr3-123767922;