rs4129886

Variant names:

• chr2-226956304-A-T
• rs4129886
• NM_001167608.3:c.857-39127A>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.857-39127A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,140 control chromosomes in the GnomAD database, including 516 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 0.078 (516 hom., cov: 32)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167608.3. 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_001167608.3	MANE Select	c.857-39127A>T		intron	N/A	NP_001161080.1	Q8TEB9-1
	RHBDD1	NM_001349069.2		c.857-39127A>T		intron	N/A	NP_001335998.1	Q8TEB9-1
	RHBDD1	NM_001349071.2		c.857-39127A>T		intron	N/A	NP_001336000.1	Q8TEB9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDD1	ENST00000392062.7	TSL:5 MANE Select	c.857-39127A>T		intron	N/A	ENSP00000375914.2	Q8TEB9-1
	RHBDD1	ENST00000341329.7	TSL:1	c.857-39127A>T		intron	N/A	ENSP00000344779.3	Q8TEB9-1
	RHBDD1	ENST00000491490.5	TSL:1	n.477-39127A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11877 AN: 152022 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.0849

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

GnomAD4 genome AF: 0.0781 AC: 11888 AN: 152140 Hom.: 516 Cov.: 32 AF XY: 0.0776 AC XY: 5774 AN XY: 74384

African (AFR) AF: 0.0494 AC: 2053 AN: 41520

American (AMR) AF: 0.0683 AC: 1044 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 296 AN: 3470

East Asian (EAS) AF: 0.180 AC: 926 AN: 5150

South Asian (SAS) AF: 0.111 AC: 534 AN: 4812

European-Finnish (FIN) AF: 0.0639 AC: 678 AN: 10606

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0900 AC: 6115 AN: 67982

Other (OTH) AF: 0.0897 AC: 189 AN: 2108

Alfa AF: 0.0724 Hom.: 47

Bravo AF: 0.0764

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.069
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4129886;

hg19: chr2-227821020;