rs62191056

Variant names:

• chr2-226914960-G-A
• rs62191056
• NM_001167608.3:c.856+609G>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+609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,146 control chromosomes in the GnomAD database, including 249 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 0.046 (249 hom., cov: 32)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 1 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.856+609G>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+609G>A		intron_variant	Intron 8 of 8	5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7019 AN: 152028 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0463 AC: 7037 AN: 152146 Hom.: 249 Cov.: 32 AF XY: 0.0464 AC XY: 3455 AN XY: 74394

African (AFR) AF: 0.0142 AC: 590 AN: 41498

American (AMR) AF: 0.0458 AC: 700 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.140 AC: 728 AN: 5184

South Asian (SAS) AF: 0.0990 AC: 477 AN: 4818

European-Finnish (FIN) AF: 0.0456 AC: 483 AN: 10594

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0554 AC: 3767 AN: 67994

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0419 Hom.: 20

Bravo AF: 0.0435

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.39
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: rs62191056; hg19: chr2-227779676;