2-226803685-A-G

Variant names:

• chr2-226803685-A-G
• rs13018009
• XM_047445998.1:c.-4280A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XM_047445998.1(RHBDD1):​c.-4280A>G variant causes a 5 prime UTR 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 XM_047445998.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 3 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]

ENSG00000272622 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	XM_047445998.1	c.-4280A>G		5_prime_UTR_variant	Exon 1 of 8		XP_047301954.1
RHBDD1	NM_001349069.2	c.-480+3463A>G		intron_variant	Intron 1 of 8		NP_001335998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.3	n.64+2330A>G		intron_variant	Intron 1 of 3	4
ENSG00000272622	ENST00000668519.2	n.256+3463A>G		intron_variant	Intron 1 of 3
ENSG00000272622	ENST00000727652.1	n.167-3801A>G		intron_variant	Intron 1 of 3

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

African (AFR) AF: 0.00373 AC: 155 AN: 41586

American (AMR) AF: 0.00954 AC: 146 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4824

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1580 AN: 68022

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.0194 Hom.: 41

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
PhyloP100		-0.0070

Splicing

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

Other links and lift over

dbSNP: rs13018009; hg19: chr2-227668401;