rs16835137

chr3-124167172-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):c.74-60818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,254 control chromosomes in the GnomAD database, including 367 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 0.070 (367 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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]

LOC105374077 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.74-60818G>A		intron_variant		ENST00000682506.1
LOC105374077	XR_924424.4	n.165G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.74-60818G>A		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10706 AN: 152136 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0704 AC: 10713 AN: 152254 Hom.: 367 Cov.: 32 AF XY: 0.0702 AC XY: 5223 AN XY: 74436

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.0948

Gnomad4 SAS AF: 0.0565

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0803

Alfa AF: 0.0599 Hom.: 31

Bravo AF: 0.0714

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16835137; hg19: chr3-123886019;