NM_001167608.3:c.856+13662A>T

Variant names:

• chr2-226928013-A-T
• rs10167086
• NM_001167608.3:c.856+13662A>T

Variant summary

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

The NM_001167608.3(RHBDD1):​c.856+13662A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,862 control chromosomes in the GnomAD database, including 16,138 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 0.46 (16138 hom., cov: 32)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.856+13662A>T		intron_variant	Intron 8 of 8	ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7	c.856+13662A>T		intron_variant	Intron 8 of 8	5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69485 AN: 151744 Hom.: 16106 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.458 AC: 69559 AN: 151862 Hom.: 16138 Cov.: 32 AF XY: 0.458 AC XY: 34027 AN XY: 74242

African (AFR) AF: 0.526 AC: 21784 AN: 41452

American (AMR) AF: 0.462 AC: 7046 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1589 AN: 3460

East Asian (EAS) AF: 0.389 AC: 2006 AN: 5162

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4824

European-Finnish (FIN) AF: 0.479 AC: 5065 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28212 AN: 67840

Other (OTH) AF: 0.422 AC: 886 AN: 2098

Alfa AF: 0.355 Hom.: 1241

Bravo AF: 0.460

Asia WGS AF: 0.463 AC: 1606 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.28
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10167086; hg19: chr2-227792729;