6-32178880-G-C

Position:

• chr6-32178880-G-C

Variant summary

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

The NM_006913.4(RNF5):​c.140+229G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,100 control chromosomes in the GnomAD database, including 1,673 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 0.14 (1673 hom., cov: 31)
• Consequence: RNF5 NM_006913.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

RNF5 (HGNC:10068): (ring finger protein 5) The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]

RNF5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF5	NM_006913.4	c.140+229G>C		intron_variant		ENST00000375094.4	NP_008844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF5	ENST00000375094.4	c.140+229G>C		intron_variant		1	NM_006913.4	ENSP00000364235.3
RNF5	ENST00000487940.1	n.215+229G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21641 AN: 151980 Hom.: 1672 Cov.: 31

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.142 AC: 21650 AN: 152100 Hom.: 1673 Cov.: 31 AF XY: 0.146 AC XY: 10820 AN XY: 74350

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0684 Hom.: 83

Bravo AF: 0.138

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9469089; hg19: chr6-32146657;