16-70336-C-A

Variant names:

• chr16-70336-C-A
• rs216614
• NM_022450.5:c.-25+2177G>T

Variant summary

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

The NM_022450.5(RHBDF1):​c.-25+2177G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 152,242 control chromosomes in the GnomAD database, including 795 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 0.073 (795 hom., cov: 33)
• Consequence: RHBDF1 NM_022450.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 7 publications found

Genes affected

RHBDF1 (HGNC:20561): (rhomboid 5 homolog 1) Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022450.5. 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
	RHBDF1	NM_022450.5	MANE Select	c.-25+2177G>T		intron	N/A	NP_071895.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBDF1	ENST00000262316.10	TSL:1 MANE Select	c.-25+2177G>T		intron	N/A	ENSP00000262316.5	Q96CC6
	RHBDF1	ENST00000944434.1		c.-25+3582G>T		intron	N/A	ENSP00000614493.1
	RHBDF1	ENST00000944435.1		c.-25+2177G>T		intron	N/A	ENSP00000614494.1

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11078 AN: 152124 Hom.: 784 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00914

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0730 AC: 11117 AN: 152242 Hom.: 795 Cov.: 33 AF XY: 0.0768 AC XY: 5713 AN XY: 74436

African (AFR) AF: 0.170 AC: 7036 AN: 41508

American (AMR) AF: 0.0915 AC: 1401 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.110 AC: 572 AN: 5188

South Asian (SAS) AF: 0.175 AC: 843 AN: 4826

European-Finnish (FIN) AF: 0.0431 AC: 458 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00914 AC: 622 AN: 68016

Other (OTH) AF: 0.0722 AC: 152 AN: 2106

Alfa AF: 0.0320 Hom.: 359

Bravo AF: 0.0799

Asia WGS AF: 0.176 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.24
PhyloP100		-0.26
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: rs216614; hg19: chr16-120334;