17-76471301-A-AC

Position:

• chr17-76471301-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001005498.4(RHBDF2):​c.*331_*332insG 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07

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 -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/exons	MANE	UniProt
RHBDF2	NM_001005498.4	c.*331_*332insG		3_prime_UTR_variant	19/19	ENST00000675367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBDF2	ENST00000675367.1	c.*331_*332insG		3_prime_UTR_variant	19/19		NM_001005498.4	P1
RHBDF2	ENST00000313080.8	c.*331_*332insG		3_prime_UTR_variant	19/19	1
RHBDF2	ENST00000590168.5	n.2254_2255insG		non_coding_transcript_exon_variant	12/12	1
RHBDF2	ENST00000591885.5	c.*331_*332insG		3_prime_UTR_variant	19/19	5		P1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6146 AN: 152094 Hom.: 407 Cov.: 33

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.: 54 Cov.: 0 AF XY: 0.00595 AC XY: 438 AN XY: 73568

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.00413

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.000155

Gnomad4 NFE exome AF: 0.000796

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0405 AC: 6161 AN: 152212 Hom.: 409 Cov.: 33 AF XY: 0.0391 AC XY: 2912 AN XY: 74436

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0316 Hom.: 31

Bravo AF: 0.0472

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Palmoplantar keratoderma-esophageal carcinoma syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58073681; hg19: chr17-74467383;