chr3-124684428-G-A

Variant names:

• chr3-124684428-G-A
• rs1708320
• NM_001388419.1:c.7377+4911G>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.7377+4911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,042 control chromosomes in the GnomAD database, including 37,004 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 0.69 (37004 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 2 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.7377+4911G>A		intron_variant	Intron 51 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.7377+4911G>A		intron_variant	Intron 51 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105092 AN: 151924 Hom.: 36952 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.692 AC: 105202 AN: 152042 Hom.: 37004 Cov.: 32 AF XY: 0.693 AC XY: 51496 AN XY: 74306

African (AFR) AF: 0.793 AC: 32900 AN: 41488

American (AMR) AF: 0.716 AC: 10936 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2497 AN: 3466

East Asian (EAS) AF: 0.902 AC: 4673 AN: 5178

South Asian (SAS) AF: 0.560 AC: 2695 AN: 4814

European-Finnish (FIN) AF: 0.639 AC: 6733 AN: 10534

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42436 AN: 67964

Other (OTH) AF: 0.685 AC: 1446 AN: 2110

Alfa AF: 0.652 Hom.: 129728

Bravo AF: 0.707

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.42
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: rs1708320; hg19: chr3-124403275; COSMIC: COSV52253265; COSMIC: COSV52253265;