ENST00000468480.5:n.768+30532G>A

Variant names:

• chr13-26184942-C-T
• rs9512144
• ENST00000468480.5:n.768+30532G>A

Variant summary

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

The ENST00000468480.5(RNF6):​n.768+30532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,942 control chromosomes in the GnomAD database, including 19,426 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 0.48 (19426 hom., cov: 31)
• Consequence: RNF6 ENST00000468480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 3 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=-1.12).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	NM_183045.1		c.408+30532G>A		intron	N/A	NP_898866.1	Q9Y252-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF6	ENST00000468480.5	TSL:1	n.768+30532G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73487 AN: 151824 Hom.: 19430 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.484 AC: 73498 AN: 151942 Hom.: 19426 Cov.: 31 AF XY: 0.476 AC XY: 35384 AN XY: 74292

African (AFR) AF: 0.293 AC: 12117 AN: 41414

American (AMR) AF: 0.387 AC: 5905 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1611 AN: 5166

South Asian (SAS) AF: 0.486 AC: 2340 AN: 4814

European-Finnish (FIN) AF: 0.564 AC: 5937 AN: 10532

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41667 AN: 67956

Other (OTH) AF: 0.511 AC: 1078 AN: 2110

Alfa AF: 0.579 Hom.: 42284

Bravo AF: 0.457

Asia WGS AF: 0.372 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.95
DANN	Benign	0.46
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs9512144; hg19: chr13-26759079;