rs6436635

Variant names:

• chr2-226800962-G-A
• rs6436635
• NM_001349069.2:c.-480+740G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-226800962-G-A
• chr2-226800962-G-C

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+740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 152,226 control chromosomes in the GnomAD database, including 639 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 0.066 (639 hom., cov: 32)
• Consequence: RHBDD1 NM_001349069.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 3 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349069.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	NM_001349069.2		c.-480+740G>A		intron	N/A	NP_001335998.1	Q8TEB9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272622	ENST00000668519.2		n.256+740G>A		intron	N/A
	ENSG00000272622	ENST00000727652.1		n.166+6122G>A		intron	N/A
	ENSG00000272622	ENST00000727653.1		n.348+4403G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10066 AN: 152108 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0662 AC: 10080 AN: 152226 Hom.: 639 Cov.: 32 AF XY: 0.0650 AC XY: 4839 AN XY: 74448

African (AFR) AF: 0.167 AC: 6930 AN: 41488

American (AMR) AF: 0.0642 AC: 983 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3472

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5186

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4826

European-Finnish (FIN) AF: 0.0275 AC: 292 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0194 AC: 1321 AN: 68016

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0367 Hom.: 456

Bravo AF: 0.0750

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.32
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: rs6436635; hg19: chr2-227665678;