XM_047436929.1:c.51+2173G>A

Variant names:

• chr17-30961177-G-A
• rs8066682
• XM_047436929.1:c.51+2173G>A

Variant summary

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

The XM_047436929.1(RNF135):​c.51+2173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,112 control chromosomes in the GnomAD database, including 10,259 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 0.21 (10259 hom., cov: 31)
• Consequence: RNF135 XM_047436929.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 2 publications found

Genes affected

RNF135 (HGNC:21158): (ring finger protein 135) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

RNF135 Gene-Disease associations (from GenCC):

• overgrowth-macrocephaly-facial dysmorphism syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• overgrowth syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF135	XM_047436929.1	c.51+2173G>A		intron_variant	Intron 1 of 4		XP_047292885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31314 AN: 151994 Hom.: 10224 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.206 AC: 31397 AN: 152112 Hom.: 10259 Cov.: 31 AF XY: 0.200 AC XY: 14868 AN XY: 74378

African (AFR) AF: 0.697 AC: 28850 AN: 41420

American (AMR) AF: 0.0802 AC: 1226 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.00698 AC: 74 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 712 AN: 68004

Other (OTH) AF: 0.156 AC: 329 AN: 2114

Alfa AF: 0.336 Hom.: 4280

Bravo AF: 0.231

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.18
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs8066682; hg19: chr17-29288195;