chr3-124369162-A-G

Variant names:

• chr3-124369162-A-G
• rs627830
• NM_001388419.1:c.1771-15683A>G

Variant summary

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

The NM_001388419.1(KALRN):​c.1771-15683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,146 control chromosomes in the GnomAD database, including 26,013 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 0.58 (26013 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 3 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 = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.1771-15683A>G		intron_variant	Intron 10 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.1771-15683A>G		intron_variant	Intron 10 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88199 AN: 152028 Hom.: 25990 Cov.: 33

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.580 AC: 88273 AN: 152146 Hom.: 26013 Cov.: 33 AF XY: 0.586 AC XY: 43588 AN XY: 74390

African (AFR) AF: 0.517 AC: 21440 AN: 41492

American (AMR) AF: 0.617 AC: 9438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3468

East Asian (EAS) AF: 0.886 AC: 4593 AN: 5182

South Asian (SAS) AF: 0.619 AC: 2989 AN: 4832

European-Finnish (FIN) AF: 0.641 AC: 6786 AN: 10582

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39506 AN: 67982

Other (OTH) AF: 0.589 AC: 1245 AN: 2112

Alfa AF: 0.580 Hom.: 13798

Bravo AF: 0.575

Asia WGS AF: 0.732 AC: 2545 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	5.6
DANN	Benign	0.37
PhyloP100		1.3
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: rs627830; hg19: chr3-124088009;