2-226904407-C-G

Position:

• chr2-226904407-C-G

Variant summary

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

The NM_001167608.3(RHBDD1):​c.567-2386C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.38 (9531 hom., cov: 20)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.567-2386C>G		intron_variant		ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7	c.567-2386C>G		intron_variant		5	NM_001167608.3	ENSP00000375914	P1
RHBDD1	ENST00000341329.7	c.567-2386C>G		intron_variant		1		ENSP00000344779	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 47205 AN: 122896 Hom.: 9524 Cov.: 20

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.384 AC: 47234 AN: 122954 Hom.: 9531 Cov.: 20 AF XY: 0.378 AC XY: 22081 AN XY: 58420

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.326

Alfa AF: 0.241 Hom.: 486

Asia WGS AF: 0.428 AC: 1398 AN: 3266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.57

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: rs4675115; hg19: chr2-227769123;