Genetic Variant RHBDF2:c.*331dupG (chr17-76471301-A-AC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001005498.4(RHBDF2):c.*331dupG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 294,462 control chromosomes in the GnomAD database, including 463 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.040 ( 409 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 54 hom. )

Consequence

RHBDF2
NM_001005498.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 17-76471301-A-AC is Benign according to our data. Variant chr17-76471301-A-AC is described in ClinVar as [Benign]. Clinvar id is 325411.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDF2	NM_001005498.4 link	c.*331dupG		3_prime_UTR_variant	Exon 19 of 19	ENST00000675367.1	NP_001005498.2	Q6PJF5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHBDF2	ENST00000675367 link	c.*331dupG	3_prime_UTR_variant	Exon 19 of 19		NM_001005498.4	ENSP00000501790.1	Q6PJF5-2
RHBDF2	ENST00000313080 link	c.*331dupG	3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000322775.3	Q6PJF5-1
RHBDF2	ENST00000590168.5 link	n.2254dupG	non_coding_transcript_exon_variant	Exon 12 of 12	1
RHBDF2	ENST00000591885 link	c.*331dupG	3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000466867.1	Q6PJF5-2

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6146

AN:

152094

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.0402

GnomAD4 exome

AF:

0.00659

AC:

938

AN:

142250

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

438

AN XY:

73568

show subpopulations

Gnomad4 AFR exome

AF:

0.126

AC:

639

AN:

5052

Gnomad4 AMR exome

AF:

0.0135

AC:

AN:

5568

Gnomad4 ASJ exome

AF:

0.00413

AC:

AN:

4606

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

9492

Gnomad4 SAS exome

AF:

0.000232

AC:

AN:

12944

Gnomad4 FIN exome

AF:

0.000155

AC:

AN:

6432

Gnomad4 NFE exome

AF:

0.000796

AC:

AN:

89202

Gnomad4 Remaining exome

AF:

0.0150

AC:

125

AN:

8324

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0405

AC:

6161

AN:

152212

Hom.:

409

Cov.:

AF XY:

0.0391

AC XY:

2912

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.137

AC:

0.136898

AN:

0.136898

Gnomad4 AMR

AF:

0.0204

AC:

0.0204002

AN:

0.0204002

Gnomad4 ASJ

AF:

0.00317

AC:

0.00317003

AN:

0.00317003

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000415

AC:

0.000414938

AN:

0.000414938

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00103

AC:

0.00102923

AN:

0.00102923

Gnomad4 OTH

AF:

0.0398

AC:

0.0397727

AN:

0.0397727

Heterozygous variant carriers

271

542

813

1084

1355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0316

Hom.:

Bravo

AF:

0.0472

Asia WGS

AF:

0.0100

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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