ENST00000468480.5:n.768+8083C>T

Variant names:

• chr13-26207391-G-A
• rs10507349
• ENST00000468480.5:n.768+8083C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000468480.5(RNF6):​n.768+8083C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,154 control chromosomes in the GnomAD database, including 3,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3460 hom., cov: 32)
• Consequence: RNF6 ENST00000468480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 35 publications found

Genes affected

RNF6 (HGNC:10069): (ring finger protein 6) The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [provided by RefSeq, Jul 2008]

RNF6 Gene-Disease associations (from GenCC):

• esophageal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468480.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	NM_183045.1		c.408+8083C>T		intron	N/A	NP_898866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	ENST00000468480.5	TSL:1	n.768+8083C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29905 AN: 152036 Hom.: 3447 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 29928 AN: 152154 Hom.: 3460 Cov.: 32 AF XY: 0.197 AC XY: 14667 AN XY: 74380

African (AFR) AF: 0.0884 AC: 3671 AN: 41528

American (AMR) AF: 0.278 AC: 4254 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2059 AN: 5168

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2141 AN: 10578

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15508 AN: 67988

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.222 Hom.: 4358

Bravo AF: 0.206

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.87
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs10507349; hg19: chr13-26781528;