rs61745397
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_001388419.1(KALRN):c.2185T>A(p.Ser729Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,614,082 control chromosomes in the GnomAD database, including 12 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 0.0029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 12 hom. )
Consequence
KALRN
NM_001388419.1 missense
NM_001388419.1 missense
Scores
4
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.23
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 -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KALRN
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0060512125).
BS2
?
High AC in GnomAd4 at 444 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KALRN | NM_001388419.1 | c.2185T>A | p.Ser729Thr | missense_variant | 13/60 | ENST00000682506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KALRN | ENST00000682506.1 | c.2185T>A | p.Ser729Thr | missense_variant | 13/60 | NM_001388419.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00292 AC: 444AN: 152090Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
444
AN:
152090
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00266 AC: 669AN: 251310Hom.: 0 AF XY: 0.00248 AC XY: 337AN XY: 135826
GnomAD3 exomes
AF:
AC:
669
AN:
251310
Hom.:
AF XY:
AC XY:
337
AN XY:
135826
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00398 AC: 5825AN: 1461874Hom.: 12 Cov.: 31 AF XY: 0.00373 AC XY: 2710AN XY: 727236
GnomAD4 exome
AF:
AC:
5825
AN:
1461874
Hom.:
Cov.:
31
AF XY:
AC XY:
2710
AN XY:
727236
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00292 AC: 444AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00310 AC XY: 231AN XY: 74424
GnomAD4 genome
?
AF:
AC:
444
AN:
152208
Hom.:
Cov.:
32
AF XY:
AC XY:
231
AN XY:
74424
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
17
ALSPAC
AF:
AC:
23
ESP6500AA
AF:
AC:
2
ESP6500EA
AF:
AC:
24
ExAC
?
AF:
AC:
357
EpiCase
AF:
EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MVP
MPC
0.59
ClinPred
T
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at