NM_001349069.2:c.-480+2054A>G

Variant names:

• chr2-226802276-A-G
• rs6725556
• NM_001349069.2:c.-480+2054A>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+2054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,292 control chromosomes in the GnomAD database, including 1,163 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 0.10 (1163 hom., cov: 32)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 11 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 (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001349069.2	c.-480+2054A>G		intron_variant	Intron 1 of 8		NP_001335998.1
RHBDD1	XM_047445998.1	c.-5689A>G		upstream_gene_variant			XP_047301954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272622	ENST00000607970.3	n.64+921A>G		intron_variant	Intron 1 of 3	4
ENSG00000272622	ENST00000668519.2	n.256+2054A>G		intron_variant	Intron 1 of 3
ENSG00000272622	ENST00000727652.1	n.167-5210A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15800 AN: 152174 Hom.: 1160 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.104 AC: 15825 AN: 152292 Hom.: 1163 Cov.: 32 AF XY: 0.102 AC XY: 7580 AN XY: 74478

African (AFR) AF: 0.206 AC: 8541 AN: 41540

American (AMR) AF: 0.0612 AC: 936 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5192

South Asian (SAS) AF: 0.144 AC: 697 AN: 4828

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4610 AN: 68030

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.0759 Hom.: 1041

Bravo AF: 0.108

Asia WGS AF: 0.0760 AC: 266 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	8.8
DANN	Benign	0.77
PhyloP100		0.79
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: rs6725556; hg19: chr2-227666992;