Genetic Variant RNF145:c.621+69A>G (chr5-159176563-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Variant links:

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]

RNF145 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
RNF145	NM_001199383.2 link	c.621+69A>G		intron_variant	Intron 5 of 10	ENST00000424310.7	NP_001186312.1	Q96MT1-1A8K9Y9Q8NDT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7 link	c.621+69A>G		intron_variant	Intron 5 of 10	1	NM_001199383.2	ENSP00000409064.2		Q96MT1-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61676

AN:

151814

Hom.:

15030

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.408

AC XY:

30276

AN XY:

74258

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over