3-124233756-C-T

Variant names:

• chr3-124233756-C-T
• rs1920629
• NM_001388419.1:c.149-1073C>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.149-1073C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,034 control chromosomes in the GnomAD database, including 2,765 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 0.14 (2765 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	NM_001388419.1	MANE Select	c.149-1073C>T		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.143-1073C>T		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.143-1073C>T		intron	N/A	NP_001309917.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.149-1073C>T		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000240874.7	TSL:1	c.143-1073C>T		intron	N/A	ENSP00000240874.3
	KALRN	ENST00000460856.5	TSL:1	c.143-1073C>T		intron	N/A	ENSP00000418611.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21206 AN: 151914 Hom.: 2765 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.140 AC: 21241 AN: 152034 Hom.: 2765 Cov.: 32 AF XY: 0.150 AC XY: 11165 AN XY: 74276

African (AFR) AF: 0.208 AC: 8599 AN: 41430

American (AMR) AF: 0.231 AC: 3530 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3304 AN: 5144

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4806

European-Finnish (FIN) AF: 0.114 AC: 1209 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2940 AN: 67992

Other (OTH) AF: 0.122 AC: 258 AN: 2114

Alfa AF: 0.0929 Hom.: 151

Bravo AF: 0.153

Asia WGS AF: 0.431 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.41
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: rs1920629; hg19: chr3-123952603;