Variant chr17-76470922-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001005498.4(RHBDF2):c.*711A>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 0.00284 in 152,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RHBDF2
NM_001005498.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.928

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:

RHBDF2 (HGNC:):

RHBDF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-76470922-T-C is Benign according to our data. Variant chr17-76470922-T-C is described in ClinVar as [Benign]. Clinvar id is 325398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 433 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDF2	NM_001005498.4 linkuse as main transcript	c.*711A>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 linkuse as main transcript	c.*711A>G	3_prime_UTR_variant	19/19		NM_001005498.4	ENSP00000501790.1	Q6PJF5-2
RHBDF2	ENST00000313080 linkuse as main transcript	c.*711A>G	3_prime_UTR_variant	19/19	1		ENSP00000322775.3	Q6PJF5-1
RHBDF2	ENST00000590168.5 linkuse as main transcript	n.2634A>G	non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

425

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00335

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152302

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00785

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.00292

Asia WGS

AF:

0.000866

AC:

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 12, 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

-0.89

CADD

Benign

0.75

DANN

Benign

0.38

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