3-124300955-C-T

Variant names:

• chr3-124300955-C-T
• rs11712619
• NM_001388419.1:c.1092+2042C>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.1092+2042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,166 control chromosomes in the GnomAD database, including 6,822 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 0.26 (6822 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.379 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.1092+2042C>T		intron	N/A	NP_001375348.1
	KALRN	NM_001024660.5		c.1086+2042C>T		intron	N/A	NP_001019831.2
	KALRN	NM_001322988.2		c.1086+2042C>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.1092+2042C>T		intron	N/A	ENSP00000508359.1
	KALRN	ENST00000240874.7	TSL:1	c.1086+2042C>T		intron	N/A	ENSP00000240874.3
	KALRN	ENST00000460856.5	TSL:1	c.1086+2042C>T		intron	N/A	ENSP00000418611.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39584 AN: 152048 Hom.: 6821 Cov.: 32

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.260 AC: 39576 AN: 152166 Hom.: 6822 Cov.: 32 AF XY: 0.256 AC XY: 19057 AN XY: 74422

African (AFR) AF: 0.0702 AC: 2916 AN: 41548

American (AMR) AF: 0.219 AC: 3343 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1449 AN: 3472

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5170

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3570 AN: 10578

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26002 AN: 67974

Other (OTH) AF: 0.251 AC: 529 AN: 2108

Alfa AF: 0.271 Hom.: 2274

Bravo AF: 0.241

Asia WGS AF: 0.106 AC: 369 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	0.0060
DANN	Benign	0.58
PhyloP100		-2.9
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: rs11712619; hg19: chr3-124019802;