rs12942767

chr17-76472470-A-Gchr17-76472470-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001005498.4(RHBDF2):c.2064+216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 657,042 control chromosomes in the GnomAD database, including 290,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (61140 hom., cov: 33)
  • Exomes 𝑓: 0.95 (229784 hom.)
• Consequence: RHBDF2 NM_001005498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.541

Genes affected

RHBDF2 (HGNC:20788): (rhomboid 5 homolog 2) Predicted to enable protein transporter activity. Predicted to be involved in negative regulation of protein secretion and regulation of epidermal growth factor receptor signaling pathway. Located in plasma membrane. Implicated in palmoplantar keratoderma-esophageal carcinoma syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-76472470-A-G is Benign according to our data. Variant chr17-76472470-A-G is described in ClinVar as [Benign]. Clinvar id is 1273628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHBDF2	NM_001005498.4	c.2064+216T>C		intron_variant		ENST00000675367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBDF2	ENST00000675367.1	c.2064+216T>C		intron_variant			NM_001005498.4	P1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134757 AN: 152106 Hom.: 61115 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.952 AC: 480486 AN: 504818 Hom.: 229784 AF XY: 0.950 AC XY: 253795 AN XY: 267140

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.914

Gnomad4 ASJ exome AF: 0.952

Gnomad4 EAS exome AF: 0.895

Gnomad4 SAS exome AF: 0.881

Gnomad4 FIN exome AF: 0.995

Gnomad4 NFE exome AF: 0.984

Gnomad4 OTH exome AF: 0.943

GnomAD4 genome AF: 0.886 AC: 134834 AN: 152224 Hom.: 61140 Cov.: 33 AF XY: 0.888 AC XY: 66059 AN XY: 74426

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.984

Gnomad4 OTH AF: 0.897

Alfa AF: 0.924 Hom.: 16487

Bravo AF: 0.872

Asia WGS AF: 0.899 AC: 3127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.79
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12942767; hg19: chr17-74468552;