rs957797

Positions:

• chr2-226812027-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349069.2(RHBDD1):​c.-91+3390T>C variant causes a intron 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: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-91+3390T>C		intron_variant			NP_001335998.1
RHBDD1	XM_047445998.1	c.-91+3390T>C		intron_variant			XP_047301954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.2	n.1551T>C		non_coding_transcript_exon_variant	4/4	4
ENSG00000272622	ENST00000668519.1	n.1582T>C		non_coding_transcript_exon_variant	4/4

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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.280

Alfa AF: 0.194 Hom.: 2890

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs957797; hg19: chr2-227676743;