2-226904407-C-G

Variant names:

• chr2-226904407-C-G
• rs4675115
• NM_001167608.3:c.567-2386C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001167608.3(RHBDD1):​c.567-2386C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.38 (9531 hom., cov: 20)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd4 at 9531 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167608.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	NM_001167608.3	MANE Select	c.567-2386C>G		intron	N/A	NP_001161080.1	Q8TEB9-1
	RHBDD1	NM_001349069.2		c.567-2386C>G		intron	N/A	NP_001335998.1	Q8TEB9-1
	RHBDD1	NM_001349071.2		c.567-2386C>G		intron	N/A	NP_001336000.1	Q8TEB9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	ENST00000392062.7	TSL:5 MANE Select	c.567-2386C>G		intron	N/A	ENSP00000375914.2	Q8TEB9-1
	RHBDD1	ENST00000341329.7	TSL:1	c.567-2386C>G		intron	N/A	ENSP00000344779.3	Q8TEB9-1
	RHBDD1	ENST00000882925.1		c.567-2386C>G		intron	N/A	ENSP00000552984.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 47205 AN: 122896 Hom.: 9524 Cov.: 20

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.384 AC: 47234 AN: 122954 Hom.: 9531 Cov.: 20 AF XY: 0.378 AC XY: 22081 AN XY: 58420

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.421 AC: 13203 AN: 31368

American (AMR) AF: 0.350 AC: 3946 AN: 11262

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1188 AN: 3098

East Asian (EAS) AF: 0.391 AC: 1613 AN: 4124

South Asian (SAS) AF: 0.428 AC: 1550 AN: 3624

European-Finnish (FIN) AF: 0.367 AC: 2401 AN: 6544

Middle Eastern (MID) AF: 0.220 AC: 48 AN: 218

European-Non Finnish (NFE) AF: 0.373 AC: 22438 AN: 60174

Other (OTH) AF: 0.326 AC: 559 AN: 1716

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.241 Hom.: 486

Asia WGS AF: 0.428 AC: 1398 AN: 3266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		0.30
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: rs4675115; hg19: chr2-227769123;