5-179966867-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_018434.6(RNF130):c.1089A>G(p.Ser363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,613,940 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (104 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (111 hom.)
• Consequence: RNF130 NM_018434.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

Genes affected

RNF130 (HGNC:18280): (ring finger protein 130) The protein encoded by this gene contains a RING finger motif and is similar to g1, a Drosophila zinc-finger protein that is expressed in mesoderm and involved in embryonic development. The expression of the mouse counterpart was found to be upregulated in myeloblastic cells following IL3 deprivation, suggesting that this gene may regulate growth factor withdrawal-induced apoptosis of myeloid precursor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-179966867-T-C is Benign according to our data. Variant chr5-179966867-T-C is described in ClinVar as [Benign]. Clinvar id is 776104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF130	NM_018434.6	c.1089A>G	p.Ser363=	synonymous_variant	7/9	ENST00000521389.6
RNF130	NM_001410829.1	c.1089A>G	p.Ser363=	synonymous_variant	7/8
RNF130	NM_001280801.2	c.1089A>G	p.Ser363=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF130	ENST00000521389.6	c.1089A>G	p.Ser363=	synonymous_variant	7/9	1	NM_018434.6	P4
RNF130	ENST00000261947.4	c.1089A>G	p.Ser363=	synonymous_variant	7/8	1		A2
RNF130	ENST00000520911.5	c.*608A>G		3_prime_UTR_variant, NMD_transcript_variant	7/9	1
RNF130	ENST00000522208.6	c.1089A>G	p.Ser363=	synonymous_variant	7/8	5		A1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3043 AN: 152036 Hom.: 102 Cov.: 33

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00542 AC: 1362 AN: 251458 Hom.: 49 AF XY: 0.00408 AC XY: 554 AN XY: 135908

Gnomad AFR exome AF: 0.0705

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000316

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00242 AC: 3542 AN: 1461786 Hom.: 111 Cov.: 31 AF XY: 0.00211 AC XY: 1538 AN XY: 727200

Gnomad4 AFR exome AF: 0.0760

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.00375

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.00520

GnomAD4 genome AF: 0.0201 AC: 3058 AN: 152154 Hom.: 104 Cov.: 33 AF XY: 0.0190 AC XY: 1414 AN XY: 74402

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0127 Hom.: 35

Bravo AF: 0.0228

Asia WGS AF: 0.00837 AC: 30 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.18
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10060093; hg19: chr5-179393867;