3-124293086-C-T

Variant names:

• chr3-124293086-C-T
• rs1444746
• NM_001388419.1:c.970-5705C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001388419.1(KALRN):​c.970-5705C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,048 control chromosomes in the GnomAD database, including 21,714 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 0.53 (21714 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.970-5705C>T		intron_variant	Intron 5 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.970-5705C>T		intron_variant	Intron 5 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80054 AN: 151930 Hom.: 21701 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.527 AC: 80115 AN: 152048 Hom.: 21714 Cov.: 32 AF XY: 0.535 AC XY: 39739 AN XY: 74306

African (AFR) AF: 0.397 AC: 16472 AN: 41468

American (AMR) AF: 0.538 AC: 8221 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3468 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3183 AN: 4806

European-Finnish (FIN) AF: 0.626 AC: 6610 AN: 10564

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38379 AN: 67980

Other (OTH) AF: 0.515 AC: 1083 AN: 2104

Alfa AF: 0.416 Hom.: 1258

Bravo AF: 0.511

Asia WGS AF: 0.654 AC: 2278 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	2.7
DANN	Benign	0.80
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1444746; hg19: chr3-124011933; COSMIC: COSV53757486;