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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.970-5705C>T		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.964-5705C>T		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.964-5705C>T		intron	N/A	NP_001309917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.970-5705C>T		intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000240874.7	TSL:1	c.964-5705C>T		intron	N/A	ENSP00000240874.3	O60229-2
	KALRN	ENST00000460856.5	TSL:1	c.964-5705C>T		intron	N/A	ENSP00000418611.1	C9IZQ6

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 v4.9

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;