rs13137105

Positions:

• chr4-75491177-A-G
• chr4-75491177-A-T

Variant summary

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

The NM_015436.4(RCHY1):​c.536+434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 159,412 control chromosomes in the GnomAD database, including 12,590 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 (12052 hom., cov: 32)
  • Exomes 𝑓: 0.37 (538 hom.)
• Consequence: RCHY1 NM_015436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCHY1	NM_015436.4	c.536+434T>C		intron_variant		ENST00000324439.10	NP_056251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCHY1	ENST00000324439.10	c.536+434T>C		intron_variant		1	NM_015436.4	ENSP00000321239	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60024 AN: 151640 Hom.: 12036 Cov.: 32

Gnomad AFR AF: 0.421

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: 0.473

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.370 AC: 2830 AN: 7654 Hom.: 538 Cov.: 0 AF XY: 0.369 AC XY: 1427 AN XY: 3872

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.396 AC: 60084 AN: 151758 Hom.: 12052 Cov.: 32 AF XY: 0.398 AC XY: 29533 AN XY: 74130

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.382

Alfa AF: 0.372 Hom.: 8847

Bravo AF: 0.395

Asia WGS AF: 0.354 AC: 1230 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.79

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: rs13137105; hg19: chr4-76416387;