rs4675096

Variant names:

• chr2-226804225-G-A
• rs4675096
• ENST00000567305.1:n.190G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000567305.1(ENSG00000261379):​n.190G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,088 control chromosomes in the GnomAD database, including 5,891 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 0.21 (5891 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ENSG00000261379 ENST00000567305.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 5 publications found

Genes affected

ENSG00000261379 (HGNC:):

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567305.1. 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.-479-3261G>A		intron	N/A	NP_001335998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000261379	ENST00000567305.1	TSL:6	n.190G>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000272622	ENST00000607970.3	TSL:4	n.64+2870G>A		intron	N/A
	ENSG00000272622	ENST00000668519.2		n.257-3261G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31646 AN: 151966 Hom.: 5864 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0887

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.209 AC: 31733 AN: 152084 Hom.: 5891 Cov.: 32 AF XY: 0.205 AC XY: 15260 AN XY: 74350

African (AFR) AF: 0.499 AC: 20662 AN: 41442

American (AMR) AF: 0.152 AC: 2316 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3468

East Asian (EAS) AF: 0.161 AC: 835 AN: 5178

South Asian (SAS) AF: 0.0846 AC: 408 AN: 4820

European-Finnish (FIN) AF: 0.0887 AC: 939 AN: 10582

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5944 AN: 68000

Other (OTH) AF: 0.165 AC: 348 AN: 2110

Alfa AF: 0.136 Hom.: 3647

Bravo AF: 0.227

Asia WGS AF: 0.174 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		0.26
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4675096; hg19: chr2-227668941;