chr3-124114767-G-A

Variant names:

• chr3-124114767-G-A
• rs1316375
• NM_001388419.1:c.73+80954G>A

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+80954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,164 control chromosomes in the GnomAD database, including 1,570 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 0.12 (1570 hom., cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KALRN	NM_001388419.1	c.73+80954G>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.73+80954G>A		intron_variant	Intron 1 of 59		NM_001388419.1	ENSP00000508359.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18511 AN: 152046 Hom.: 1567 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.122 AC: 18515 AN: 152164 Hom.: 1570 Cov.: 32 AF XY: 0.130 AC XY: 9655 AN XY: 74362

African (AFR) AF: 0.0893 AC: 3709 AN: 41530

American (AMR) AF: 0.182 AC: 2791 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2348 AN: 5158

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4814

European-Finnish (FIN) AF: 0.142 AC: 1499 AN: 10578

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6334 AN: 68002

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.113 Hom.: 483

Bravo AF: 0.124

Asia WGS AF: 0.325 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DANN	Benign	0.46
PhyloP100		-0.70
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: rs1316375; hg19: chr3-123833614; COSMIC: COSV53757269;