rs1158012

Variant names:

• chr3-124238548-A-G
• rs1158012
• NM_001388419.1:c.263+3605A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-124238548-A-G
• chr3-124238548-A-T

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+3605A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,016 control chromosomes in the GnomAD database, including 19,752 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 0.51 (19752 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.263+3605A>G		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+3605A>G		intron_variant	Intron 3 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76758 AN: 151898 Hom.: 19761 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.505 AC: 76785 AN: 152016 Hom.: 19752 Cov.: 32 AF XY: 0.509 AC XY: 37805 AN XY: 74304

African (AFR) AF: 0.399 AC: 16545 AN: 41462

American (AMR) AF: 0.525 AC: 8022 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1799 AN: 3466

East Asian (EAS) AF: 0.660 AC: 3409 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2715 AN: 4810

European-Finnish (FIN) AF: 0.568 AC: 6004 AN: 10568

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36571 AN: 67960

Other (OTH) AF: 0.503 AC: 1062 AN: 2112

Alfa AF: 0.517 Hom.: 9925

Bravo AF: 0.498

Asia WGS AF: 0.596 AC: 2075 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	2.1
DANN	Benign	0.65
PhyloP100		-0.090
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: rs1158012; hg19: chr3-123957395;