chr2-226803685-A-G

Position:

• chr2-226803685-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001349069.2(RHBDD1):​c.-480+3463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 152,330 control chromosomes in the GnomAD database, including 26 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 0.015 (26 hom., cov: 33)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2225/152330) while in subpopulation NFE AF= 0.0232 (1580/68022). AF 95% confidence interval is 0.0223. There are 26 homozygotes in gnomad4. There are 1024 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDD1	XM_047445998.1	c.-4280A>G		5_prime_UTR_variant	1/8		XP_047301954.1
RHBDD1	NM_001349069.2	c.-480+3463A>G		intron_variant			NP_001335998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.2	n.46+2330A>G		intron_variant		4
ENSG00000272622	ENST00000668519.1	n.77+3463A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2225 AN: 152212 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0146 AC: 2225 AN: 152330 Hom.: 26 Cov.: 33 AF XY: 0.0137 AC XY: 1024 AN XY: 74492

Gnomad4 AFR AF: 0.00373

Gnomad4 AMR AF: 0.00954

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0120 Hom.: 3

Bravo AF: 0.0144

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13018009; hg19: chr2-227668401;