NM_001388419.1:c.969+1342G>A

Variant names:

• chr3-124270597-G-A
• rs9868324
• NM_001388419.1:c.969+1342G>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.969+1342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,752 control chromosomes in the GnomAD database, including 2,913 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 0.19 (2913 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 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.969+1342G>A		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.963+1342G>A		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.963+1342G>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.969+1342G>A		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000240874.7	TSL:1	c.963+1342G>A		intron	N/A	ENSP00000240874.3
	KALRN	ENST00000460856.5	TSL:1	c.963+1342G>A		intron	N/A	ENSP00000418611.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29529 AN: 151636 Hom.: 2909 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.195 AC: 29551 AN: 151752 Hom.: 2913 Cov.: 32 AF XY: 0.199 AC XY: 14753 AN XY: 74158

African (AFR) AF: 0.198 AC: 8186 AN: 41396

American (AMR) AF: 0.219 AC: 3339 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1036 AN: 5148

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2332 AN: 10474

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12110 AN: 67888

Other (OTH) AF: 0.199 AC: 419 AN: 2104

Alfa AF: 0.180 Hom.: 320

Bravo AF: 0.192

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.20
PhyloP100		0.98
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: rs9868324; hg19: chr3-123989444; COSMIC: COSV53757401; COSMIC: COSV53757401;