3-124219370-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388419.1(KALRN):​c.74-8620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,026 control chromosomes in the GnomAD database, including 22,822 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 0.54 ( 22822 hom., cov: 32)

Consequence

KALRN
NM_001388419.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KALRNNM_001388419.1 linkuse as main transcriptc.74-8620C>T intron_variant ENST00000682506.1 NP_001375348.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KALRNENST00000682506.1 linkuse as main transcriptc.74-8620C>T intron_variant NM_001388419.1 ENSP00000508359 A2

Frequencies

GnomAD3 genomes
AF:
0.543
AC:
82443
AN:
151906
Hom.:
22804
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.441
Gnomad AMI
AF:
0.564
Gnomad AMR
AF:
0.588
Gnomad ASJ
AF:
0.618
Gnomad EAS
AF:
0.443
Gnomad SAS
AF:
0.521
Gnomad FIN
AF:
0.515
Gnomad MID
AF:
0.582
Gnomad NFE
AF:
0.603
Gnomad OTH
AF:
0.555
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.543
AC:
82488
AN:
152026
Hom.:
22822
Cov.:
32
AF XY:
0.539
AC XY:
40040
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.441
Gnomad4 AMR
AF:
0.589
Gnomad4 ASJ
AF:
0.618
Gnomad4 EAS
AF:
0.442
Gnomad4 SAS
AF:
0.521
Gnomad4 FIN
AF:
0.515
Gnomad4 NFE
AF:
0.603
Gnomad4 OTH
AF:
0.550
Alfa
AF:
0.562
Hom.:
4079
Bravo
AF:
0.545
Asia WGS
AF:
0.478
AC:
1666
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
6.6
DANN
Benign
0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1444754; hg19: chr3-123938217; API