3-124103440-G-A

Variant names:

• chr3-124103440-G-A
• rs13075202
• NM_001388419.1:c.73+69627G>A

Variant summary

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

The NM_001388419.1(KALRN):​c.73+69627G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,028 control chromosomes in the GnomAD database, including 30,069 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 0.60 (30069 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 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.73+69627G>A		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.67+8536G>A		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.67+8536G>A		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.73+69627G>A		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000240874.7	TSL:1	c.67+8536G>A		intron	N/A	ENSP00000240874.3
	KALRN	ENST00000460856.5	TSL:1	c.67+8536G>A		intron	N/A	ENSP00000418611.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90868 AN: 151908 Hom.: 30061 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.598 AC: 90893 AN: 152028 Hom.: 30069 Cov.: 32 AF XY: 0.596 AC XY: 44264 AN XY: 74324

African (AFR) AF: 0.287 AC: 11892 AN: 41464

American (AMR) AF: 0.648 AC: 9899 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2531 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2732 AN: 5174

South Asian (SAS) AF: 0.645 AC: 3097 AN: 4802

European-Finnish (FIN) AF: 0.701 AC: 7410 AN: 10568

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51198 AN: 67962

Other (OTH) AF: 0.620 AC: 1304 AN: 2102

Alfa AF: 0.580 Hom.: 3106

Bravo AF: 0.580

Asia WGS AF: 0.542 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.44
PhyloP100		0.28
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: rs13075202; hg19: chr3-123822287; COSMIC: COSV53767434;