2-226923876-T-C

Position:

• chr2-226923876-T-C

Variant summary

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

The NM_001167608.3(RHBDD1):​c.856+9525T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,678 control chromosomes in the GnomAD database, including 19,783 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 0.50 (19783 hom., cov: 30)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.856+9525T>C		intron_variant		ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7	c.856+9525T>C		intron_variant		5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75688 AN: 151560 Hom.: 19738 Cov.: 30

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.500 AC: 75781 AN: 151678 Hom.: 19783 Cov.: 30 AF XY: 0.499 AC XY: 36970 AN XY: 74120

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.450

Alfa AF: 0.322 Hom.: 774

Bravo AF: 0.506

Asia WGS AF: 0.491 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1114562; hg19: chr2-227788592;