3-124105614-T-G

Variant names:

• chr3-124105614-T-G
• rs13067260
• NM_001388419.1:c.73+71801T>G

Variant summary

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

The NM_001388419.1(KALRN):​c.73+71801T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 151,802 control chromosomes in the GnomAD database, including 60,362 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 0.89 (60362 hom., cov: 31)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.73+71801T>G		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.73+71801T>G		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134528 AN: 151684 Hom.: 60327 Cov.: 31

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.887 AC: 134617 AN: 151802 Hom.: 60362 Cov.: 31 AF XY: 0.890 AC XY: 66040 AN XY: 74200

African (AFR) AF: 0.736 AC: 30374 AN: 41290

American (AMR) AF: 0.924 AC: 14094 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3283 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5150 AN: 5150

South Asian (SAS) AF: 0.988 AC: 4758 AN: 4814

European-Finnish (FIN) AF: 0.936 AC: 9910 AN: 10584

Middle Eastern (MID) AF: 0.901 AC: 263 AN: 292

European-Non Finnish (NFE) AF: 0.944 AC: 64132 AN: 67940

Other (OTH) AF: 0.891 AC: 1873 AN: 2102

Alfa AF: 0.920 Hom.: 14028

Bravo AF: 0.879

Asia WGS AF: 0.974 AC: 3387 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	11
DANN	Benign	0.55
PhyloP100		0.61
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: rs13067260; hg19: chr3-123824461;