rs484936

Variant names:

• chr3-124506244-A-G
• rs484936
• NM_001388419.1:c.4935+9831A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-124506244-A-G
• chr3-124506244-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.4935+9831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,930 control chromosomes in the GnomAD database, including 16,788 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 0.45 (16788 hom., cov: 31)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.4935+9831A>G		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.4929+9831A>G		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.4929+9831A>G		intron	N/A	NP_001309917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.4935+9831A>G		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.4929+9831A>G		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.4902+9831A>G		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69090 AN: 151812 Hom.: 16773 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.455 AC: 69122 AN: 151930 Hom.: 16788 Cov.: 31 AF XY: 0.462 AC XY: 34318 AN XY: 74254

African (AFR) AF: 0.281 AC: 11663 AN: 41452

American (AMR) AF: 0.523 AC: 7985 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3470

East Asian (EAS) AF: 0.626 AC: 3222 AN: 5150

South Asian (SAS) AF: 0.428 AC: 2058 AN: 4812

European-Finnish (FIN) AF: 0.629 AC: 6634 AN: 10544

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34480 AN: 67932

Other (OTH) AF: 0.452 AC: 952 AN: 2104

Alfa AF: 0.485 Hom.: 10084

Bravo AF: 0.437

Asia WGS AF: 0.493 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		0.32
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: rs484936; hg19: chr3-124225091;