rs869585

Variant names:

• chr3-124035117-G-A
• rs869585
• NM_001388419.1:c.73+1304G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001388419.1(KALRN):​c.73+1304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,196 control chromosomes in the GnomAD database, including 30 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 0.014 (30 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• 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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2194/152196) while in subpopulation NFE AF = 0.0225 (1531/67994). AF 95% confidence interval is 0.0216. There are 30 homozygotes in GnomAd4. There are 1068 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2194 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.73+1304G>A		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001388417.1		c.73+1304G>A		intron	N/A	NP_001375346.1
	KALRN	NM_001388418.1		c.73+1304G>A		intron	N/A	NP_001375347.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.73+1304G>A		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000683571.1		c.73+1304G>A		intron	N/A	ENSP00000506888.1	A0A804HI42
	KALRN	ENST00000682861.1		c.73+1304G>A		intron	N/A	ENSP00000506756.1	A0A804HHT5

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2195 AN: 152078 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0143

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

GnomAD4 genome AF: 0.0144 AC: 2194 AN: 152196 Hom.: 30 Cov.: 32 AF XY: 0.0143 AC XY: 1068 AN XY: 74432

African (AFR) AF: 0.00344 AC: 143 AN: 41514

American (AMR) AF: 0.0157 AC: 240 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4820

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0225 AC: 1531 AN: 67994

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0163 Hom.: 19

Bravo AF: 0.0139

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.6
DANN	Benign	0.59
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs869585; hg19: chr3-123753964;