chr13-26184942-C-T

Position:

• chr13-26184942-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183045.1(RNF6):​c.408+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 NM_183045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

Genes affected

RNF6 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF6	NM_183045.1	c.408+30532G>A		intron_variant			NP_898866.1
RNF6	XM_011535178.3	c.408+30532G>A		intron_variant			XP_011533480.1
RNF6	XM_047430498.1	c.408+30532G>A		intron_variant			XP_047286454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF6	ENST00000468480.5	n.768+30532G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.511

Alfa AF: 0.594 Hom.: 35068

Bravo AF: 0.457

Asia WGS AF: 0.372 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9512144; hg19: chr13-26759079;