rs869585

Positions:

• chr3-124035117-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.73+1304G>A		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.73+1304G>A		intron_variant			NM_001388419.1	A2
KALRN	ENST00000682861.1	c.73+1304G>A		intron_variant
KALRN	ENST00000683571.1	c.73+1304G>A		intron_variant

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

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0194 Hom.: 12

Bravo AF: 0.0139

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869585; hg19: chr3-123753964;