5-159191257-T-C

Variant names:

• chr5-159191257-T-C
• rs1897565
• NM_001199383.2:c.293+3459A>G

Variant summary

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

The NM_001199383.2(RNF145):​c.293+3459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,000 control chromosomes in the GnomAD database, including 12,846 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 0.38 (12846 hom., cov: 31)
• Consequence: RNF145 NM_001199383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199383.2. 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
	RNF145	NM_001199383.2	MANE Select	c.293+3459A>G		intron	N/A	NP_001186312.1
	RNF145	NM_001199380.2		c.383+3459A>G		intron	N/A	NP_001186309.1
	RNF145	NM_144726.3		c.377+3459A>G		intron	N/A	NP_653327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF145	ENST00000424310.7	TSL:1 MANE Select	c.293+3459A>G		intron	N/A	ENSP00000409064.2
	RNF145	ENST00000518802.5	TSL:1	c.383+3459A>G		intron	N/A	ENSP00000430955.1
	RNF145	ENST00000274542.6	TSL:2	c.377+3459A>G		intron	N/A	ENSP00000274542.2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57973 AN: 151882 Hom.: 12825 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.382 AC: 58042 AN: 152000 Hom.: 12846 Cov.: 31 AF XY: 0.383 AC XY: 28480 AN XY: 74312

African (AFR) AF: 0.594 AC: 24622 AN: 41424

American (AMR) AF: 0.434 AC: 6636 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1895 AN: 5182

South Asian (SAS) AF: 0.448 AC: 2155 AN: 4814

European-Finnish (FIN) AF: 0.256 AC: 2706 AN: 10574

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17636 AN: 67942

Other (OTH) AF: 0.404 AC: 853 AN: 2114

Alfa AF: 0.310 Hom.: 2036

Bravo AF: 0.403

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.40
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: rs1897565; hg19: chr5-158618265;