chr5-159177955-G-A

Variant names:

• chr5-159177955-G-A
• rs10076782
• NM_001199383.2:c.386-1088C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199383.2(RNF145):​c.386-1088C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,816 control chromosomes in the GnomAD database, including 14,982 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 (14982 hom., cov: 33)
• Consequence: RNF145 NM_001199383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 28 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF145	NM_001199383.2	c.386-1088C>T		intron_variant	Intron 4 of 10	ENST00000424310.7	NP_001186312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7	c.386-1088C>T		intron_variant	Intron 4 of 10	1	NM_001199383.2	ENSP00000409064.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61547 AN: 151698 Hom.: 14955 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.406 AC: 61628 AN: 151816 Hom.: 14982 Cov.: 33 AF XY: 0.407 AC XY: 30215 AN XY: 74184

African (AFR) AF: 0.670 AC: 27775 AN: 41468

American (AMR) AF: 0.448 AC: 6834 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1134 AN: 3462

East Asian (EAS) AF: 0.369 AC: 1909 AN: 5180

South Asian (SAS) AF: 0.443 AC: 2130 AN: 4806

European-Finnish (FIN) AF: 0.257 AC: 2708 AN: 10536

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17800 AN: 67808

Other (OTH) AF: 0.424 AC: 894 AN: 2108

Alfa AF: 0.318 Hom.: 27545

Bravo AF: 0.431

Asia WGS AF: 0.471 AC: 1636 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.11
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: rs10076782; hg19: chr5-158604963;