rs9813731

Variant names:

• chr3-124267191-A-G
• rs9813731
• NM_001388419.1:c.457-1552A>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.457-1552A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,322 control chromosomes in the GnomAD database, including 240 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 0.050 (240 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 0 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0797 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.457-1552A>G		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.451-1552A>G		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.451-1552A>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.457-1552A>G		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.451-1552A>G		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.451-1552A>G		intron	N/A	ENSP00000418611.1	C9IZQ6

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7685 AN: 152204 Hom.: 241 Cov.: 33

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0504 AC: 7678 AN: 152322 Hom.: 240 Cov.: 33 AF XY: 0.0501 AC XY: 3735 AN XY: 74488

African (AFR) AF: 0.0554 AC: 2301 AN: 41560

American (AMR) AF: 0.0393 AC: 602 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.0863 AC: 448 AN: 5190

South Asian (SAS) AF: 0.0709 AC: 342 AN: 4824

European-Finnish (FIN) AF: 0.0358 AC: 380 AN: 10622

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0477 AC: 3245 AN: 68034

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0519 Hom.: 28

Bravo AF: 0.0497

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.2
DANN	Benign	0.89
PhyloP100		0.085
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: rs9813731; hg19: chr3-123986038;