Variant chr17-76471014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001005498.4(RHBDF2):c.*619A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 153,164 control chromosomes in the GnomAD database, including 929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 929 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 0 hom. )

Consequence

RHBDF2
NM_001005498.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.446

Variant links:

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]

RHBDF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-76471014-T-C is Benign according to our data. Variant chr17-76471014-T-C is described in ClinVar as [Benign]. Clinvar id is 325402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDF2	NM_001005498.4 link	c.*619A>G		3_prime_UTR_variant	19/19	ENST00000675367.1	NP_001005498.2	Q6PJF5-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHBDF2	ENST00000675367 link	c.*619A>G	3_prime_UTR_variant	19/19		NM_001005498.4	ENSP00000501790.1	Q6PJF5-2
RHBDF2	ENST00000313080 link	c.*619A>G	3_prime_UTR_variant	19/19	1		ENSP00000322775.3	Q6PJF5-1
RHBDF2	ENST00000590168.5 link	n.2542A>G	non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes

AF:

0.0764

AC:

11621

AN:

152096

Hom.:

923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0815

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.0618

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0774

GnomAD4 exome

AF:

0.00947

AC:

AN:

950

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

AN XY:

488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.0385

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00667

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0766

AC:

11654

AN:

152214

Hom.:

929

Cov.:

AF XY:

0.0759

AC XY:

5648

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0814

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.0620

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.0780

Alfa

AF:

0.0491

Hom.:

194

Bravo

AF:

0.0848

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Palmoplantar keratoderma-esophageal carcinoma syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.0

DANN

Benign

0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over