rs2289843
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1
The NM_001388419.1(KALRN):c.4104A>T(p.Ala1368=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,607,274 control chromosomes in the GnomAD database, including 19,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.12 ( 1918 hom., cov: 32)
Exomes 𝑓: 0.13 ( 17894 hom. )
Consequence
KALRN
NM_001388419.1 splice_region, synonymous
NM_001388419.1 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.948
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 3-124477247-A-T is Benign according to our data. Variant chr3-124477247-A-T is described in ClinVar as [Benign]. Clinvar id is 3060446.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.948 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KALRN | NM_001388419.1 | c.4104A>T | p.Ala1368= | splice_region_variant, synonymous_variant | 27/60 | ENST00000682506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KALRN | ENST00000682506.1 | c.4104A>T | p.Ala1368= | splice_region_variant, synonymous_variant | 27/60 | NM_001388419.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.123 AC: 18652AN: 152082Hom.: 1907 Cov.: 32
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GnomAD3 exomes AF: 0.172 AC: 43123AN: 251102Hom.: 5636 AF XY: 0.165 AC XY: 22392AN XY: 135704
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GnomAD4 exome AF: 0.133 AC: 193792AN: 1455078Hom.: 17894 Cov.: 29 AF XY: 0.132 AC XY: 95876AN XY: 724346
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GnomAD4 genome ? AF: 0.123 AC: 18668AN: 152196Hom.: 1918 Cov.: 32 AF XY: 0.132 AC XY: 9853AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KALRN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at