rs10933155

Variant names:

• chr2-226822191-C-T
• rs10933155
• NM_001349069.2:c.-91+13554C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-91+13554C>T		intron_variant	Intron 3 of 8		NP_001335998.1
RHBDD1	XM_047445998.1	c.-91+13554C>T		intron_variant	Intron 2 of 7		XP_047301954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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

African (AFR) AF: 0.171 AC: 7104 AN: 41474

American (AMR) AF: 0.573 AC: 8768 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2507 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1257 AN: 5178

South Asian (SAS) AF: 0.563 AC: 2713 AN: 4822

European-Finnish (FIN) AF: 0.638 AC: 6733 AN: 10556

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46188 AN: 67990

Other (OTH) AF: 0.544 AC: 1148 AN: 2110

Alfa AF: 0.619 Hom.: 91698

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
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs10933155; hg19: chr2-227686907;