Variant 17-76471122-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001005498.4(RHBDF2):c.*511G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 160,072 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 98 hom., cov: 33)

Exomes 𝑓: 0.033 ( 11 hom. )

Consequence

RHBDF2
NM_001005498.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.159

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-76471122-C-T is Benign according to our data. Variant chr17-76471122-C-T is described in ClinVar as [Benign]. Clinvar id is 325408.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0344 (5238/152176) while in subpopulation NFE AF= 0.0508 (3457/68006). AF 95% confidence interval is 0.0494. There are 98 homozygotes in gnomad4. There are 2465 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHBDF2	NM_001005498.4 linkuse as main transcript	c.*511G>A		3_prime_UTR_variant	19/19	ENST00000675367.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBDF2	ENST00000675367.1 linkuse as main transcript	c.*511G>A	3_prime_UTR_variant	19/19		NM_001005498.4	P1	Q6PJF5-2
RHBDF2	ENST00000313080.8 linkuse as main transcript	c.*511G>A	3_prime_UTR_variant	19/19	1			Q6PJF5-1
RHBDF2	ENST00000590168.5 linkuse as main transcript	n.2434G>A	non_coding_transcript_exon_variant	12/12	1
RHBDF2	ENST00000591885.5 linkuse as main transcript	c.*511G>A	3_prime_UTR_variant	19/19	5		P1	Q6PJF5-2

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5239

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0392

GnomAD4 exome

AF:

0.0332

AC:

262

AN:

7896

Hom.:

Cov.:

AF XY:

0.0322

AC XY:

133

AN XY:

4126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0180

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0149

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0472

Gnomad4 OTH exome

AF:

0.0439

GnomAD4 genome

AF:

0.0344

AC:

5238

AN:

152176

Hom.:

Cov.:

AF XY:

0.0331

AC XY:

2465

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.0431

Gnomad4 NFE

AF:

0.0508

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0456

Hom.:

Bravo

AF:

0.0334

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.3

DANN

Benign

0.67

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

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