chr3-124237749-T-C

Variant names:

• chr3-124237749-T-C
• rs4678095
• NM_001388419.1:c.263+2806T>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.263+2806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,048 control chromosomes in the GnomAD database, including 13,399 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 0.39 (13399 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.263+2806T>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.263+2806T>C		intron_variant	Intron 3 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59961 AN: 151928 Hom.: 13399 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.394 AC: 59981 AN: 152048 Hom.: 13399 Cov.: 32 AF XY: 0.390 AC XY: 29013 AN XY: 74308

African (AFR) AF: 0.187 AC: 7772 AN: 41482

American (AMR) AF: 0.451 AC: 6891 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5154

South Asian (SAS) AF: 0.362 AC: 1739 AN: 4808

European-Finnish (FIN) AF: 0.429 AC: 4540 AN: 10572

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.512 AC: 34795 AN: 67984

Other (OTH) AF: 0.445 AC: 940 AN: 2112

Alfa AF: 0.477 Hom.: 30523

Bravo AF: 0.388

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.42
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: rs4678095; hg19: chr3-123956596;