rs17511627

Variant names:

• chr13-26150190-A-C
• rs17511627
• ENST00000468480.5:n.769-17739T>G

Variant summary

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

The ENST00000468480.5(RNF6):​n.769-17739T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,692 control chromosomes in the GnomAD database, including 2,711 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 0.19 (2711 hom., cov: 30)
• Consequence: RNF6 ENST00000468480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 12 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]

ATP8A2P3 (HGNC:42641): (ATPase phospholipid transporting 8A2 pseudogene 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A2P3		n.26150190A>C		intragenic_variant
RNF6	NM_183045.1	c.409-17739T>G		intron_variant	Intron 5 of 5		NP_898866.1
RNF6	XM_011535178.3	c.409-17739T>G		intron_variant	Intron 5 of 5		XP_011533480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF6	ENST00000468480.5	n.769-17739T>G		intron_variant	Intron 5 of 5	1
ATP8A2P3	ENST00000426792.2	n.199+618T>G		intron_variant	Intron 2 of 16	6

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28101 AN: 151576 Hom.: 2717 Cov.: 30

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.185 AC: 28096 AN: 151692 Hom.: 2711 Cov.: 30 AF XY: 0.187 AC XY: 13850 AN XY: 74088

African (AFR) AF: 0.164 AC: 6776 AN: 41380

American (AMR) AF: 0.234 AC: 3561 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3460

East Asian (EAS) AF: 0.158 AC: 811 AN: 5132

South Asian (SAS) AF: 0.193 AC: 928 AN: 4802

European-Finnish (FIN) AF: 0.207 AC: 2166 AN: 10466

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.185 AC: 12545 AN: 67924

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.185 Hom.: 8289

Bravo AF: 0.189

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.54
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs17511627; hg19: chr13-26724328;