rs957797

Variant names:

• chr2-226812027-T-C
• rs957797
• ENST00000607970.3:n.1569T>C

Variant summary

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

The ENST00000607970.3(ENSG00000272622):​n.1569T>C 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 0.318 in 152,124 control chromosomes in the GnomAD database, including 11,283 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 0.32 (11283 hom., cov: 32)
• Consequence: ENSG00000272622 ENST00000607970.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 4 publications found

Genes affected

ENSG00000272622 (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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-91+3390T>C		intron_variant	Intron 3 of 8		NP_001335998.1
RHBDD1	XM_047445998.1	c.-91+3390T>C		intron_variant	Intron 2 of 7		XP_047301954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.3	n.1569T>C		non_coding_transcript_exon_variant	Exon 4 of 4	4
ENSG00000272622	ENST00000668519.2	n.1761T>C		non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000272622	ENST00000727652.1	n.1671T>C		non_coding_transcript_exon_variant	Exon 4 of 4
ENSG00000272622	ENST00000727653.1	n.1853T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48285 AN: 152006 Hom.: 11228 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.318 AC: 48404 AN: 152124 Hom.: 11283 Cov.: 32 AF XY: 0.312 AC XY: 23169 AN XY: 74378

African (AFR) AF: 0.665 AC: 27594 AN: 41468

American (AMR) AF: 0.231 AC: 3530 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3464

East Asian (EAS) AF: 0.295 AC: 1521 AN: 5164

South Asian (SAS) AF: 0.230 AC: 1110 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12008 AN: 68008

Other (OTH) AF: 0.280 AC: 591 AN: 2110

Alfa AF: 0.200 Hom.: 3681

Bravo AF: 0.340

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs957797; hg19: chr2-227676743;