rs2037483
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000258774.10(HUS1):c.761-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 867,144 control chromosomes in the GnomAD database, including 104,727 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 0.46 ( 16791 hom., cov: 33)
Exomes 𝑓: 0.49 ( 87936 hom. )
Consequence
HUS1
ENST00000258774.10 intron
ENST00000258774.10 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.14
Genes affected
HUS1 (HGNC:5309): (HUS1 checkpoint clamp component) The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
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 (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HUS1 | NM_004507.4 | c.761-87C>T | intron_variant | ENST00000258774.10 | NP_004498.1 | |||
HUS1 | NM_001363683.2 | c.698-87C>T | intron_variant | NP_001350612.1 | ||||
HUS1 | NR_037917.2 | n.915-87C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HUS1 | ENST00000258774.10 | c.761-87C>T | intron_variant | 1 | NM_004507.4 | ENSP00000258774 | P1 | |||
HUS1 | ENST00000432325.5 | c.698-87C>T | intron_variant | 5 | ENSP00000416588 | |||||
HUS1 | ENST00000458191.5 | c.698-87C>T | intron_variant, NMD_transcript_variant | 2 | ENSP00000400727 |
Frequencies
GnomAD3 genomes AF: 0.460 AC: 69860AN: 151910Hom.: 16794 Cov.: 33
GnomAD3 genomes
AF:
AC:
69860
AN:
151910
Hom.:
Cov.:
33
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:
GnomAD4 exome AF: 0.490 AC: 350325AN: 715116Hom.: 87936 AF XY: 0.485 AC XY: 183038AN XY: 377248
GnomAD4 exome
AF:
AC:
350325
AN:
715116
Hom.:
AF XY:
AC XY:
183038
AN XY:
377248
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: 0.460 AC: 69875AN: 152028Hom.: 16791 Cov.: 33 AF XY: 0.465 AC XY: 34531AN XY: 74314
GnomAD4 genome
AF:
AC:
69875
AN:
152028
Hom.:
Cov.:
33
AF XY:
AC XY:
34531
AN XY:
74314
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:
Asia WGS
AF:
AC:
1658
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at