rs1473247

Positions:

• chr5-159176563-T-C

Variant summary

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

The NM_001199383.2(RNF145):​c.621+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 927,510 control chromosomes in the GnomAD database, including 54,818 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 0.41 (15057 hom., cov: 32)
  • Exomes 𝑓: 0.30 (39761 hom.)
• Consequence: RNF145 NM_001199383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF145	NM_001199383.2	c.621+69A>G		intron_variant		ENST00000424310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF145	ENST00000424310.7	c.621+69A>G		intron_variant		1	NM_001199383.2	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61676 AN: 151814 Hom.: 15030 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.304 AC: 235873 AN: 775578 Hom.: 39761 AF XY: 0.308 AC XY: 123358 AN XY: 400754

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.406 AC: 61757 AN: 151932 Hom.: 15057 Cov.: 32 AF XY: 0.408 AC XY: 30276 AN XY: 74258

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.425

Alfa AF: 0.300 Hom.: 9517

Bravo AF: 0.432

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.38

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: rs1473247; hg19: chr5-158603571; COSMIC: COSV50876319; COSMIC: COSV50876319;