rs2251495

chr9-122880408-G-Achr9-122880408-G-C

Variant summary

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

The NM_001100588.3(RC3H2):c.960+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 675,220 control chromosomes in the GnomAD database, including 223,144 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 0.74 (43597 hom., cov: 31)
  • Exomes 𝑓: 0.81 (179547 hom.)
• Consequence: RC3H2 NM_001100588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

Genes affected

RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RC3H2	NM_001100588.3	c.960+186C>T		intron_variant		ENST00000357244.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RC3H2	ENST00000357244.7	c.960+186C>T		intron_variant		5	NM_001100588.3	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112228 AN: 151934 Hom.: 43607 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.814 AC: 425666 AN: 523166 Hom.: 179547 Cov.: 6 AF XY: 0.821 AC XY: 229577 AN XY: 279600

Gnomad4 AFR exome AF: 0.533

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.836

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.887

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.793

GnomAD4 genome AF: 0.738 AC: 112232 AN: 152054 Hom.: 43597 Cov.: 31 AF XY: 0.733 AC XY: 54527 AN XY: 74348

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.754

Alfa AF: 0.758 Hom.: 3836

Bravo AF: 0.709

Asia WGS AF: 0.586 AC: 2042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.0
Dann	Benign	0.46

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: rs2251495; hg19: chr9-125642687; COSMIC: COSV59012528; COSMIC: COSV59012528;