rs449511

Positions:

• chr5-180000400-A-G
• chr5-180000400-A-T

Variant summary

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

The NM_018434.6(RNF130):​c.693+12661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,940 control chromosomes in the GnomAD database, including 15,338 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 0.44 (15338 hom., cov: 31)
• Consequence: RNF130 NM_018434.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF130	NM_018434.6	c.693+12661T>C		intron_variant		ENST00000521389.6	NP_060904.2
RNF130	NM_001280801.2	c.693+12661T>C		intron_variant			NP_001267730.1
RNF130	NM_001410829.1	c.693+12661T>C		intron_variant			NP_001397758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF130	ENST00000521389.6	c.693+12661T>C		intron_variant		1	NM_018434.6	ENSP00000430237	P4
RNF130	ENST00000261947.4	c.693+12661T>C		intron_variant		1		ENSP00000261947	A2
RNF130	ENST00000520911.5	c.*212+12661T>C		intron_variant, NMD_transcript_variant		1		ENSP00000430999
RNF130	ENST00000522208.6	c.693+12661T>C		intron_variant		5		ENSP00000429509	A1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67230 AN: 151822 Hom.: 15319 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.443 AC: 67303 AN: 151940 Hom.: 15338 Cov.: 31 AF XY: 0.442 AC XY: 32814 AN XY: 74262

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.413

Alfa AF: 0.417 Hom.: 2318

Bravo AF: 0.442

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.68

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: rs449511; hg19: chr5-179427400;