2-226809848-C-G

Variant names:

• chr2-226809848-C-G
• rs956115
• NM_001349069.2:c.-91+1211C>G

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+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
• Publications: 11 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]

ENSG00000272622 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349069.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	NM_001349069.2		c.-91+1211C>G		intron	N/A	NP_001335998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272622	ENST00000607970.3	TSL:4	n.454-1064C>G		intron	N/A
	ENSG00000272622	ENST00000668519.2		n.646-1064C>G		intron	N/A
	ENSG00000272622	ENST00000727652.1		n.556-1064C>G		intron	N/A

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

African (AFR) AF: 0.231 AC: 9593 AN: 41510

American (AMR) AF: 0.0864 AC: 1320 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3466

East Asian (EAS) AF: 0.133 AC: 689 AN: 5186

South Asian (SAS) AF: 0.125 AC: 603 AN: 4828

European-Finnish (FIN) AF: 0.0463 AC: 491 AN: 10602

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6100 AN: 67990

Other (OTH) AF: 0.125 AC: 264 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.65
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs956115; hg19: chr2-227674564;