Genetic Variant RCHY1:c.536+434T>A (chr4-75491177-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015436.4(RCHY1):c.536+434T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCHY1
NM_015436.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06

Publications

11 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RCHY1	NM_015436.4	MANE Select	c.536+434T>A	intron	N/A	NP_056251.2	Q96PM5-1
RCHY1	NM_001009922.3		c.510-476T>A	intron	N/A	NP_001009922.1	Q96PM5-2
RCHY1	NM_001278538.2		c.470+434T>A	intron	N/A	NP_001265467.1	Q96PM5-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RCHY1	ENST00000324439.10	TSL:1 MANE Select	c.536+434T>A	intron	N/A	ENSP00000321239.5	Q96PM5-1
RCHY1	ENST00000513257.5	TSL:1	c.510-476T>A	intron	N/A	ENSP00000421084.1	Q96PM5-2
RCHY1	ENST00000380840.6	TSL:1	c.416+434T>A	intron	N/A	ENSP00000370220.2	Q96PM5-7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151708

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

7698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

3896

African (AFR)

AF:

0.00

AC:

AN:

268

American (AMR)

AF:

0.00

AC:

AN:

392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

270

East Asian (EAS)

AF:

0.00

AC:

AN:

220

South Asian (SAS)

AF:

0.00

AC:

AN:

240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5572

Other (OTH)

AF:

0.00

AC:

AN:

476

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74046

African (AFR)

AF:

0.00

AC:

AN:

41320

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67838

Other (OTH)

AF:

0.00

AC:

AN:

2084

Alfa

AF:

0.00

Hom.:

15839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over