3-124326456-G-A

Variant names:

• chr3-124326456-G-A
• rs7620580
• NM_001388419.1:c.1284+285G>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.1284+285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,096 control chromosomes in the GnomAD database, including 50,497 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 0.80 (50497 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.1284+285G>A		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.1278+285G>A		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.1278+285G>A		intron	N/A	NP_001309917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.1284+285G>A		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000240874.7	TSL:1	c.1278+285G>A		intron	N/A	ENSP00000240874.3
	KALRN	ENST00000460856.5	TSL:1	c.1278+285G>A		intron	N/A	ENSP00000418611.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122004 AN: 151978 Hom.: 50466 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.803 AC: 122086 AN: 152096 Hom.: 50497 Cov.: 32 AF XY: 0.805 AC XY: 59885 AN XY: 74356

African (AFR) AF: 0.587 AC: 24319 AN: 41404

American (AMR) AF: 0.831 AC: 12713 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4018 AN: 5176

South Asian (SAS) AF: 0.892 AC: 4304 AN: 4824

European-Finnish (FIN) AF: 0.906 AC: 9602 AN: 10600

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.904 AC: 61484 AN: 68018

Other (OTH) AF: 0.809 AC: 1703 AN: 2104

Alfa AF: 0.865 Hom.: 11694

Bravo AF: 0.788

Asia WGS AF: 0.828 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.39
PhyloP100		-0.78
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: rs7620580; hg19: chr3-124045303;