chr2-226819112-A-G

Variant names:

• chr2-226819112-A-G
• rs13417106
• NM_001349069.2:c.-91+10475A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001349069.2(RHBDD1):​c.-91+10475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,066 control chromosomes in the GnomAD database, including 8,348 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 0.24 (8348 hom., cov: 30)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349069.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	NM_001349069.2		c.-91+10475A>G		intron	N/A	NP_001335998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36637 AN: 151950 Hom.: 8310 Cov.: 30

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.242 AC: 36735 AN: 152066 Hom.: 8348 Cov.: 30 AF XY: 0.237 AC XY: 17622 AN XY: 74358

African (AFR) AF: 0.604 AC: 25025 AN: 41452

American (AMR) AF: 0.165 AC: 2516 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3470

East Asian (EAS) AF: 0.161 AC: 834 AN: 5166

South Asian (SAS) AF: 0.146 AC: 703 AN: 4814

European-Finnish (FIN) AF: 0.0886 AC: 938 AN: 10588

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0887 AC: 6033 AN: 67982

Other (OTH) AF: 0.191 AC: 402 AN: 2106

Alfa AF: 0.340 Hom.: 3045

Bravo AF: 0.263

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.67
PhyloP100		0.56

Splicing

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

Other links and lift over

dbSNP: rs13417106; hg19: chr2-227683828;