rs16835137

Variant names:

• chr3-124167172-G-A
• rs16835137
• NM_001388419.1:c.74-60818G>A

Variant summary

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

The NM_001388419.1(KALRN):​c.74-60818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,254 control chromosomes in the GnomAD database, including 367 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 (367 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• 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]

LOC105374077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.74-60818G>A		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.74-60818G>A		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10706 AN: 152136 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0704 AC: 10713 AN: 152254 Hom.: 367 Cov.: 32 AF XY: 0.0702 AC XY: 5223 AN XY: 74436

African (AFR) AF: 0.0769 AC: 3193 AN: 41538

American (AMR) AF: 0.0655 AC: 1002 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.0948 AC: 491 AN: 5178

South Asian (SAS) AF: 0.0565 AC: 272 AN: 4816

European-Finnish (FIN) AF: 0.0648 AC: 688 AN: 10618

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4545 AN: 68020

Other (OTH) AF: 0.0803 AC: 170 AN: 2116

Alfa AF: 0.0645 Hom.: 167

Bravo AF: 0.0714

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		-0.069
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: rs16835137; hg19: chr3-123886019;