rs216614

Positions:

• chr16-70336-C-A
• chr16-70336-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

RHBDF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDF1	NM_022450.5	c.-25+2177G>T		intron_variant		ENST00000262316.10	NP_071895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBDF1	ENST00000262316.10	c.-25+2177G>T		intron_variant		1	NM_022450.5	ENSP00000262316.5
RHBDF1	ENST00000450643.5	c.-24-5297G>T		intron_variant		4		ENSP00000408915.1
RHBDF1	ENST00000472390.1	n.90-5297G>T		intron_variant		4
RHBDF1	ENST00000487201.1	n.109+2177G>T		intron_variant		5

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

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.00914

Gnomad4 OTH AF: 0.0722

Alfa AF: 0.0201 Hom.: 127

Bravo AF: 0.0799

Asia WGS AF: 0.176 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs216614; hg19: chr16-120334;