rs2043270

Variant names:

• chr5-159170973-A-G
• rs2043270
• NM_001199383.2:c.798-1154T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF145	NM_001199383.2	c.798-1154T>C		intron_variant	Intron 6 of 10	ENST00000424310.7	NP_001186312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7	c.798-1154T>C		intron_variant	Intron 6 of 10	1	NM_001199383.2	ENSP00000409064.2

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

African (AFR) AF: 0.0467 AC: 1939 AN: 41560

American (AMR) AF: 0.0698 AC: 1068 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5186

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4826

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5495 AN: 67996

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0751 Hom.: 270

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
PhyloP100		-0.10
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: rs2043270; hg19: chr5-158597981;