rs956115

Positions:

• chr2-226809848-C-G
• chr2-226809848-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+1211C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,186 control chromosomes in the GnomAD database, including 1,573 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 0.13 (1573 hom., cov: 32)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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]

ENSG00000272622 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-91+1211C>G		intron_variant			NP_001335998.1
RHBDD1	XM_047445998.1	c.-91+1211C>G		intron_variant			XP_047301954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.2	n.436-1064C>G		intron_variant		4
ENSG00000272622	ENST00000668519.1	n.467-1064C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19356 AN: 152068 Hom.: 1558 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.128 AC: 19407 AN: 152186 Hom.: 1573 Cov.: 32 AF XY: 0.123 AC XY: 9171 AN XY: 74406

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0983 Hom.: 119

Bravo AF: 0.135

Asia WGS AF: 0.146 AC: 506 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs956115; hg19: chr2-227674564;