rs6725330

Variant names:

• chr2-226802141-A-G
• rs6725330
• NM_001349069.2:c.-480+1919A>G

Variant summary

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

The NM_001349069.2(RHBDD1):​c.-480+1919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,116 control chromosomes in the GnomAD database, including 1,664 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 0.14 (1664 hom., cov: 32)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 15 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]

ENSG00000272622 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-480+1919A>G		intron_variant	Intron 1 of 8		NP_001335998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.3	n.64+786A>G		intron_variant	Intron 1 of 3	4
ENSG00000272622	ENST00000668519.2	n.256+1919A>G		intron_variant	Intron 1 of 3
ENSG00000272622	ENST00000727652.1	n.167-5345A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21293 AN: 151998 Hom.: 1659 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0907

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.140 AC: 21324 AN: 152116 Hom.: 1664 Cov.: 32 AF XY: 0.140 AC XY: 10408 AN XY: 74360

African (AFR) AF: 0.195 AC: 8075 AN: 41438

American (AMR) AF: 0.120 AC: 1833 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3468

East Asian (EAS) AF: 0.0911 AC: 473 AN: 5190

South Asian (SAS) AF: 0.245 AC: 1178 AN: 4812

European-Finnish (FIN) AF: 0.0720 AC: 762 AN: 10586

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7653 AN: 68010

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.128 Hom.: 2633

Bravo AF: 0.144

Asia WGS AF: 0.166 AC: 578 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.70
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6725330; hg19: chr2-227666857;