rs7627053

Variant names:

• chr3-124203417-G-A
• rs7627053
• NM_001388419.1:c.74-24573G>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.74-24573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,252 control chromosomes in the GnomAD database, including 295 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 0.064 (295 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.74-24573G>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.74-24573G>A		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9667 AN: 152134 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0636 AC: 9685 AN: 152252 Hom.: 295 Cov.: 32 AF XY: 0.0638 AC XY: 4750 AN XY: 74458

African (AFR) AF: 0.0674 AC: 2799 AN: 41532

American (AMR) AF: 0.0676 AC: 1034 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.00733 AC: 38 AN: 5182

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4824

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0651 AC: 4426 AN: 68014

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0612 Hom.: 103

Bravo AF: 0.0642

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.065
DANN	Benign	0.56
PhyloP100		-2.0
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: rs7627053; hg19: chr3-123922264;