chr3-124057759-T-C

Position:

• chr3-124057759-T-C

Variant summary

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

The NM_001388419.1(KALRN):​c.73+23946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 152,182 control chromosomes in the GnomAD database, including 1,036 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 0.075 (1036 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KALRN	NM_001388419.1	c.73+23946T>C		intron_variant		ENST00000682506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KALRN	ENST00000682506.1	c.73+23946T>C		intron_variant			NM_001388419.1	A2
KALRN	ENST00000682861.1	c.73+23946T>C		intron_variant
KALRN	ENST00000683571.1	c.73+23946T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11382 AN: 152064 Hom.: 1030 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0728

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

GnomAD4 genome AF: 0.0749 AC: 11398 AN: 152182 Hom.: 1036 Cov.: 32 AF XY: 0.0827 AC XY: 6154 AN XY: 74390

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0725

Alfa AF: 0.0645 Hom.: 548

Bravo AF: 0.0820

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
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: rs16835038; hg19: chr3-123776606;