rs1864271

Variant names:

• chr2-226915550-G-C
• rs1864271
• NM_001167608.3:c.856+1199G>C

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+1199G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,098 control chromosomes in the GnomAD database, including 15,008 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 0.42 (15008 hom., cov: 32)
• Consequence: RHBDD1 NM_001167608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.856+1199G>C		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+1199G>C		intron_variant	Intron 8 of 8	5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63472 AN: 151978 Hom.: 14968 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.418 AC: 63580 AN: 152098 Hom.: 15008 Cov.: 32 AF XY: 0.409 AC XY: 30426 AN XY: 74340

African (AFR) AF: 0.639 AC: 26503 AN: 41480

American (AMR) AF: 0.308 AC: 4698 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3472

East Asian (EAS) AF: 0.152 AC: 790 AN: 5188

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4816

European-Finnish (FIN) AF: 0.235 AC: 2487 AN: 10580

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24334 AN: 67970

Other (OTH) AF: 0.437 AC: 923 AN: 2110

Alfa AF: 0.370 Hom.: 1624

Bravo AF: 0.431

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.59
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: rs1864271; hg19: chr2-227780266;