3-124049075-T-G

Variant names:

• chr3-124049075-T-G
• rs2332690
• NM_001388419.1:c.73+15262T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.73+15262T>G		intron_variant	Intron 1 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.73+15262T>G		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1
KALRN	ENST00000683571.1	c.73+15262T>G		intron_variant	Intron 1 of 3			ENSP00000506888.1
KALRN	ENST00000682861.1	c.73+15262T>G		intron_variant	Intron 1 of 1			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

African (AFR) AF: 0.580 AC: 24046 AN: 41466

American (AMR) AF: 0.741 AC: 11336 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2900 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2698 AN: 5170

South Asian (SAS) AF: 0.746 AC: 3587 AN: 4806

European-Finnish (FIN) AF: 0.785 AC: 8319 AN: 10594

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57100 AN: 68006

Other (OTH) AF: 0.732 AC: 1548 AN: 2116

Alfa AF: 0.799 Hom.: 134222

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
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs2332690; hg19: chr3-123767922;