NM_001388419.1:c.5183-11045G>C

Variant names:

• chr3-124621375-G-C
• rs10512627
• NM_001388419.1:c.5183-11045G>C

Variant summary

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

The NM_001388419.1(KALRN):​c.5183-11045G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,062 control chromosomes in the GnomAD database, including 14,550 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 0.43 (14550 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 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.5183-11045G>C		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.5177-11045G>C		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.5177-11045G>C		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.5183-11045G>C		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000291478.9	TSL:1	c.86-11045G>C		intron	N/A	ENSP00000291478.4
	KALRN	ENST00000454902.1	TSL:1	c.86-11045G>C		intron	N/A	ENSP00000400064.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65838 AN: 151944 Hom.: 14534 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.433 AC: 65889 AN: 152062 Hom.: 14550 Cov.: 33 AF XY: 0.430 AC XY: 31943 AN XY: 74322

African (AFR) AF: 0.397 AC: 16465 AN: 41468

American (AMR) AF: 0.368 AC: 5619 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1565 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1470 AN: 5186

South Asian (SAS) AF: 0.467 AC: 2246 AN: 4812

European-Finnish (FIN) AF: 0.460 AC: 4858 AN: 10554

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32130 AN: 67982

Other (OTH) AF: 0.435 AC: 919 AN: 2114

Alfa AF: 0.461 Hom.: 8975

Bravo AF: 0.424

Asia WGS AF: 0.404 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.82
PhyloP100		-0.12
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: rs10512627; hg19: chr3-124340222; COSMIC: COSV52252531;