rs1444768

Variant names:

• chr3-124205075-G-A
• rs1444768
• NM_001388419.1:c.74-22915G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-124205075-G-A
• chr3-124205075-G-C
• chr3-124205075-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.74-22915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,044 control chromosomes in the GnomAD database, including 22,734 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 0.52 (22734 hom., cov: 33)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.74-22915G>A		intron_variant	Intron 1 of 59	ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1	c.74-22915G>A		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78534 AN: 151926 Hom.: 22726 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.517 AC: 78568 AN: 152044 Hom.: 22734 Cov.: 33 AF XY: 0.516 AC XY: 38322 AN XY: 74320

African (AFR) AF: 0.240 AC: 9954 AN: 41426

American (AMR) AF: 0.575 AC: 8794 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2289 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2358 AN: 5164

South Asian (SAS) AF: 0.528 AC: 2545 AN: 4820

European-Finnish (FIN) AF: 0.609 AC: 6438 AN: 10576

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44351 AN: 67988

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.612 Hom.: 123943

Bravo AF: 0.503

Asia WGS AF: 0.478 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		0.10
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: rs1444768; hg19: chr3-123923922;