rs10933155

Positions:

• chr2-226822191-C-T

Variant summary

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

The NM_001349069.2(RHBDD1):​c.-91+13554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,102 control chromosomes in the GnomAD database, including 23,353 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 0.51 (23353 hom., cov: 33)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

Genes affected

RHBDD1 (HGNC:23081): (rhomboid domain containing 1) Enables serine-type endopeptidase activity. Involved in several processes, including cellular response to unfolded protein; membrane protein proteolysis; and positive regulation of protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-91+13554C>T		intron_variant			NP_001335998.1
RHBDD1	XM_047445998.1	c.-91+13554C>T		intron_variant			XP_047301954.1
		n.226822191C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77226 AN: 151982 Hom.: 23364 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.508 AC: 77206 AN: 152102 Hom.: 23353 Cov.: 33 AF XY: 0.507 AC XY: 37724 AN XY: 74364

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.544

Alfa AF: 0.652 Hom.: 43043

Bravo AF: 0.488

Asia WGS AF: 0.370 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10933155; hg19: chr2-227686907;