rs9873910

Variant names:

• chr3-124512361-G-A
• rs9873910
• NM_001388419.1:c.4935+15948G>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.4935+15948G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,224 control chromosomes in the GnomAD database, including 1,395 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 0.13 (1395 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• 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]

ENSG00000297494 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 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+15948G>A		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.4929+15948G>A		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.4929+15948G>A		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+15948G>A		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.4930-6039G>A		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.4903-6039G>A		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19584 AN: 152106 Hom.: 1394 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.129 AC: 19586 AN: 152224 Hom.: 1395 Cov.: 32 AF XY: 0.126 AC XY: 9412 AN XY: 74430

African (AFR) AF: 0.137 AC: 5691 AN: 41542

American (AMR) AF: 0.106 AC: 1624 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.194 AC: 936 AN: 4824

European-Finnish (FIN) AF: 0.0714 AC: 757 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9305 AN: 68004

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.129 Hom.: 218

Bravo AF: 0.131

Asia WGS AF: 0.0860 AC: 300 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.58
PhyloP100		-0.79
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: rs9873910; hg19: chr3-124231208;