rs9833095

chr3-124228786-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.148+722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,248 control chromosomes in the GnomAD database, including 277 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 0.058 (277 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.148+722G>A		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.148+722G>A		intron_variant			NM_001388419.1	A2

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8841 AN: 152130 Hom.: 276 Cov.: 33

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0512

Gnomad OTH AF: 0.0692

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

GnomAD4 genome AF: 0.0581 AC: 8852 AN: 152248 Hom.: 277 Cov.: 33 AF XY: 0.0594 AC XY: 4424 AN XY: 74436

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.0632

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0485 Hom.: 16

Bravo AF: 0.0589

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.34
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9833095; hg19: chr3-123947633;