chr3-124206748-T-A

Position:

• chr3-124206748-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001388419.1(KALRN):​c.74-21242T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,288 control chromosomes in the GnomAD database, including 308 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 0.066 (308 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.74-21242T>A		intron_variant		ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.74-21242T>A		intron_variant			NM_001388419.1	ENSP00000508359	A2

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10097 AN: 152170 Hom.: 309 Cov.: 33

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0663 AC: 10101 AN: 152288 Hom.: 308 Cov.: 33 AF XY: 0.0671 AC XY: 5001 AN XY: 74482

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0652

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.0736

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0589 Hom.: 28

Bravo AF: 0.0661

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6438833; hg19: chr3-123925595;