NM_001388419.1:c.74-42646T>C

Variant names:

• chr3-124185344-T-C
• rs16835162
• NM_001388419.1:c.74-42646T>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.74-42646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,220 control chromosomes in the GnomAD database, including 2,688 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 0.17 (2688 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.74-42646T>C		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.74-42646T>C		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25952 AN: 152102 Hom.: 2688 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.170 AC: 25950 AN: 152220 Hom.: 2688 Cov.: 32 AF XY: 0.179 AC XY: 13325 AN XY: 74392

African (AFR) AF: 0.103 AC: 4282 AN: 41572

American (AMR) AF: 0.240 AC: 3666 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2650 AN: 5174

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4816

European-Finnish (FIN) AF: 0.212 AC: 2240 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10712 AN: 67990

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.164 Hom.: 1865

Bravo AF: 0.170

Asia WGS AF: 0.366 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		0.75
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: rs16835162; hg19: chr3-123904191;