rs16835038

Variant summary

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

The NM_001388419.1(KALRN):​c.73+23946T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 152,182 control chromosomes in the GnomAD database, including 1,036 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 0.075 ( 1036 hom., cov: 32)

Consequence

KALRN
NM_001388419.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KALRNNM_001388419.1 linkuse as main transcriptc.73+23946T>C intron_variant ENST00000682506.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KALRNENST00000682506.1 linkuse as main transcriptc.73+23946T>C intron_variant NM_001388419.1 A2
KALRNENST00000682861.1 linkuse as main transcriptc.73+23946T>C intron_variant
KALRNENST00000683571.1 linkuse as main transcriptc.73+23946T>C intron_variant

Frequencies

GnomAD3 genomes
AF:
0.0749
AC:
11382
AN:
152064
Hom.:
1030
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0137
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.201
Gnomad ASJ
AF:
0.0504
Gnomad EAS
AF:
0.415
Gnomad SAS
AF:
0.137
Gnomad FIN
AF:
0.0994
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.0522
Gnomad OTH
AF:
0.0728
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0749
AC:
11398
AN:
152182
Hom.:
1036
Cov.:
32
AF XY:
0.0827
AC XY:
6154
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0137
Gnomad4 AMR
AF:
0.202
Gnomad4 ASJ
AF:
0.0504
Gnomad4 EAS
AF:
0.415
Gnomad4 SAS
AF:
0.137
Gnomad4 FIN
AF:
0.0994
Gnomad4 NFE
AF:
0.0522
Gnomad4 OTH
AF:
0.0725
Alfa
AF:
0.0645
Hom.:
548
Bravo
AF:
0.0820
Asia WGS
AF:
0.249
AC:
865
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.1
DANN
Benign
0.74

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: rs16835038; hg19: chr3-123776606; API