rs13134862

chr4-75500686-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015436.4(RCHY1):c.327-6507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,850 control chromosomes in the GnomAD database, including 12,095 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 0.40 (12095 hom., cov: 32)
• Consequence: RCHY1 NM_015436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCHY1	NM_015436.4	c.327-6507C>T		intron_variant		ENST00000324439.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCHY1	ENST00000324439.10	c.327-6507C>T		intron_variant		1	NM_015436.4	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60154 AN: 151732 Hom.: 12079 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60214 AN: 151850 Hom.: 12095 Cov.: 32 AF XY: 0.399 AC XY: 29615 AN XY: 74172

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.383

Alfa AF: 0.391 Hom.: 2065

Bravo AF: 0.395

Asia WGS AF: 0.358 AC: 1244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.47
Dann	Benign	0.16

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

Other links and lift over

dbSNP: rs13134862; hg19: chr4-76425896;