rs2279784

Variant names:

• chr3-124562757-G-A
• rs2279784
• NM_001388419.1:c.4936-86G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-124562757-G-A
• chr3-124562757-G-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.4936-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,175,368 control chromosomes in the GnomAD database, including 12,279 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 (2493 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9786 hom.)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 10 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]

LOC105374076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.4936-86G>A		intron_variant	Intron 33 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.4936-86G>A		intron_variant	Intron 33 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21628 AN: 150336 Hom.: 2481 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.112 AC: 114698 AN: 1024914 Hom.: 9786 Cov.: 16 AF XY: 0.115 AC XY: 56796 AN XY: 495470

African (AFR) AF: 0.110 AC: 2403 AN: 21940

American (AMR) AF: 0.376 AC: 8458 AN: 22516

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 1458 AN: 11278

East Asian (EAS) AF: 0.630 AC: 7437 AN: 11806

South Asian (SAS) AF: 0.203 AC: 12953 AN: 63906

European-Finnish (FIN) AF: 0.129 AC: 2480 AN: 19290

Middle Eastern (MID) AF: 0.215 AC: 851 AN: 3954

European-Non Finnish (NFE) AF: 0.0882 AC: 73478 AN: 833358

Other (OTH) AF: 0.141 AC: 5180 AN: 36866

GnomAD4 genome AF: 0.144 AC: 21667 AN: 150454 Hom.: 2493 Cov.: 32 AF XY: 0.155 AC XY: 11383 AN XY: 73334

African (AFR) AF: 0.113 AC: 4598 AN: 40800

American (AMR) AF: 0.275 AC: 4164 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3462

East Asian (EAS) AF: 0.623 AC: 3186 AN: 5112

South Asian (SAS) AF: 0.222 AC: 1050 AN: 4734

European-Finnish (FIN) AF: 0.144 AC: 1477 AN: 10244

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6295 AN: 67666

Other (OTH) AF: 0.149 AC: 312 AN: 2098

Alfa AF: 0.111 Hom.: 1959

Bravo AF: 0.155

Asia WGS AF: 0.387 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.35
PhyloP100		-0.55
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: rs2279784; hg19: chr3-124281604; COSMIC: COSV62566012;