3-124250578-A-C

Variant names:

• chr3-124250578-A-C
• rs4678100
• NM_001388419.1:c.264-13920A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.264-13920A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,284 control chromosomes in the GnomAD database, including 400 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 0.070 (400 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.264-13920A>C		intron_variant	Intron 3 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.264-13920A>C		intron_variant	Intron 3 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10615 AN: 152166 Hom.: 400 Cov.: 33

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0922

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

GnomAD4 genome AF: 0.0697 AC: 10611 AN: 152284 Hom.: 400 Cov.: 33 AF XY: 0.0681 AC XY: 5069 AN XY: 74470

African (AFR) AF: 0.0679 AC: 2822 AN: 41556

American (AMR) AF: 0.0618 AC: 946 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3470

East Asian (EAS) AF: 0.0847 AC: 438 AN: 5174

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4818

European-Finnish (FIN) AF: 0.0413 AC: 439 AN: 10630

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0738 AC: 5018 AN: 68018

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.0736 Hom.: 182

Bravo AF: 0.0709

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		-0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4678100; hg19: chr3-123969425;