NM_018434.6:c.693+12661T>C

Variant names:

• chr5-180000400-A-G
• rs449511
• NM_018434.6:c.693+12661T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018434.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF130	NM_018434.6	MANE Select	c.693+12661T>C		intron	N/A	NP_060904.2
	RNF130	NM_001410829.1		c.693+12661T>C		intron	N/A	NP_001397758.1
	RNF130	NM_001280801.2		c.693+12661T>C		intron	N/A	NP_001267730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF130	ENST00000521389.6	TSL:1 MANE Select	c.693+12661T>C		intron	N/A	ENSP00000430237.1
	RNF130	ENST00000261947.4	TSL:1	c.693+12661T>C		intron	N/A	ENSP00000261947.4
	RNF130	ENST00000520911.5	TSL:1	n.*212+12661T>C		intron	N/A	ENSP00000430999.1

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

African (AFR) AF: 0.563 AC: 23327 AN: 41410

American (AMR) AF: 0.385 AC: 5878 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1483 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2259 AN: 5164

South Asian (SAS) AF: 0.275 AC: 1322 AN: 4816

European-Finnish (FIN) AF: 0.454 AC: 4781 AN: 10530

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26983 AN: 67964

Other (OTH) AF: 0.413 AC: 872 AN: 2112

Alfa AF: 0.422 Hom.: 2455

Bravo AF: 0.442

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.90
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: rs449511; hg19: chr5-179427400;