5-179973847-C-A

Variant names:

• chr5-179973847-C-A
• rs3756616
• NM_018434.6:c.849-3341G>T

Variant summary

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

The NM_018434.6(RNF130):​c.849-3341G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,084 control chromosomes in the GnomAD database, including 20,002 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 (20002 hom., cov: 32)
• Consequence: RNF130 NM_018434.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF130	NM_018434.6	c.849-3341G>T		intron_variant	Intron 5 of 8	ENST00000521389.6	NP_060904.2
RNF130	NM_001410829.1	c.849-3341G>T		intron_variant	Intron 5 of 7		NP_001397758.1
RNF130	NM_001280801.2	c.849-3341G>T		intron_variant	Intron 5 of 7		NP_001267730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6	c.849-3341G>T		intron_variant	Intron 5 of 8	1	NM_018434.6	ENSP00000430237.1
RNF130	ENST00000520911.5	n.*368-3341G>T		intron_variant	Intron 5 of 8	1		ENSP00000430999.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72263 AN: 151966 Hom.: 19965 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.476 AC: 72348 AN: 152084 Hom.: 20002 Cov.: 32 AF XY: 0.468 AC XY: 34781 AN XY: 74342

African (AFR) AF: 0.772 AC: 32020 AN: 41466

American (AMR) AF: 0.422 AC: 6445 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3470

East Asian (EAS) AF: 0.152 AC: 786 AN: 5180

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4822

European-Finnish (FIN) AF: 0.353 AC: 3730 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25099 AN: 67980

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.391 Hom.: 21048

Bravo AF: 0.494

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.84
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3756616; hg19: chr5-179400847;