Variant 4-75514275-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000324439.10(RCHY1):c.12G>A(p.Thr4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,612,422 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 7 hom., cov: 33)

Exomes 𝑓: 0.011 ( 128 hom. )

Consequence

RCHY1
ENST00000324439.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0860

Variant links:

Genes affected

RCHY1 (HGNC:17479): (ring finger and CHY zinc finger domain containing 1) The protein encoded by this gene has ubiquitin ligase activity. It mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including tumor protein 53, histone deacetylase 1, and cyclin-dependent kinase inhibitor 1B, thus regulating their levels and cell cycle progression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2013]

RCHY1 links:

THAP6 (HGNC:23189): (THAP domain containing 6) Predicted to enable DNA binding activity and metal ion binding activity. Located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

THAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 4-75514275-C-T is Benign according to our data. Variant chr4-75514275-C-T is described in ClinVar as [Benign]. Clinvar id is 775069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.086 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCHY1	NM_015436.4 linkuse as main transcript	c.12G>A	p.Thr4=	synonymous_variant	1/9	ENST00000324439.10	NP_056251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCHY1	ENST00000324439.10 linkuse as main transcript	c.12G>A	p.Thr4=	synonymous_variant	1/9	1	NM_015436.4	ENSP00000321239	P1	Q96PM5-1

Frequencies

GnomAD3 genomes

AF:

0.00819

AC:

1246

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00857

AC:

2152

AN:

251240

Hom.:

AF XY:

0.00853

AC XY:

1159

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00729

Gnomad ASJ exome

AF:

0.0167

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.0133

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0114

AC:

16710

AN:

1460138

Hom.:

128

Cov.:

AF XY:

0.0114

AC XY:

8250

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00747

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00240

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00818

AC:

1245

AN:

152284

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

547

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00840

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0147

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over