2-226937638-G-A

Variant names:

• chr2-226937638-G-A
• rs4675124
• NM_001167608.3:c.856+23287G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167608.3(RHBDD1):​c.856+23287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,864 control chromosomes in the GnomAD database, including 26,597 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 0.58 (26597 hom., cov: 32)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.856+23287G>A		intron_variant	Intron 8 of 8	ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7	c.856+23287G>A		intron_variant	Intron 8 of 8	5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88539 AN: 151746 Hom.: 26550 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.584 AC: 88644 AN: 151864 Hom.: 26597 Cov.: 32 AF XY: 0.582 AC XY: 43218 AN XY: 74214

African (AFR) AF: 0.733 AC: 30373 AN: 41452

American (AMR) AF: 0.545 AC: 8297 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3468

East Asian (EAS) AF: 0.568 AC: 2926 AN: 5154

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5743 AN: 10536

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34495 AN: 67890

Other (OTH) AF: 0.547 AC: 1152 AN: 2106

Alfa AF: 0.524 Hom.: 34153

Bravo AF: 0.588

Asia WGS AF: 0.644 AC: 2242 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	3.3
DANN	Benign	0.57
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4675124; hg19: chr2-227802354;