rs2043270

chr5-159170973-A-G

Variant summary

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

The NM_001199383.2(RNF145):c.798-1154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,256 control chromosomes in the GnomAD database, including 371 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 0.067 (371 hom., cov: 32)
• Consequence: RNF145 NM_001199383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF145	NM_001199383.2	c.798-1154T>C		intron_variant		ENST00000424310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF145	ENST00000424310.7	c.798-1154T>C		intron_variant		1	NM_001199383.2	P1

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10207 AN: 152138 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0671 AC: 10217 AN: 152256 Hom.: 371 Cov.: 32 AF XY: 0.0654 AC XY: 4867 AN XY: 74442

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0757 Hom.: 231

Bravo AF: 0.0660

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.8
Dann	Benign	0.84

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: rs2043270; hg19: chr5-158597981;