rs2010099

Variant names:

• chr3-124581410-C-G
• rs2010099
• NM_001388419.1:c.5182+18321C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-124581410-C-G
• chr3-124581410-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001388419.1(KALRN):​c.5182+18321C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 141,702 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000035 (0 hom., cov: 30)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 12 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]

LOC105374076 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.5182+18321C>G		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.5176+18321C>G		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.5176+18321C>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.5182+18321C>G		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000360013.7	TSL:5	c.5176+18321C>G		intron	N/A	ENSP00000353109.3	O60229-1
	KALRN	ENST00000354186.8	TSL:5	c.5080+18321C>G		intron	N/A	ENSP00000346122.4	H7BXZ5

Frequencies

GnomAD3 genomes AF: 0.0000353 AC: 5 AN: 141670 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000353 AC: 5 AN: 141702 Hom.: 0 Cov.: 30 AF XY: 0.0000291 AC XY: 2 AN XY: 68626

African (AFR) AF: 0.000103 AC: 4 AN: 38698

American (AMR) AF: 0.0000719 AC: 1 AN: 13906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3310

East Asian (EAS) AF: 0.00 AC: 0 AN: 4744

South Asian (SAS) AF: 0.00 AC: 0 AN: 4484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64558

Other (OTH) AF: 0.00 AC: 0 AN: 1934

Alfa AF: 0.00 Hom.: 2102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.85
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2010099; hg19: chr3-124300257;