Variant chr4-153712582-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173662.4(RNF175):c.765-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,594,806 control chromosomes in the GnomAD database, including 33,407 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3445 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29962 hom. )

Consequence

RNF175
NM_173662.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.5802

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

RNF175 (HGNC:27735): (ring finger protein 175) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF175 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=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF175	NM_173662.4 linkuse as main transcript	c.765-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000347063.9	NP_775933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF175	ENST00000347063.9 linkuse as main transcript	c.765-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_173662.4	ENSP00000340979	P1	Q8N4F7-1
RNF175	ENST00000513656.5 linkuse as main transcript	c.*512-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3		ENSP00000421761

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32390

AN:

152006

Hom.:

3441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.208

AC:

50631

AN:

243170

Hom.:

5397

AF XY:

0.207

AC XY:

27296

AN XY:

131666

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.201

AC:

290661

AN:

1442680

Hom.:

29962

Cov.:

AF XY:

0.202

AC XY:

144865

AN XY:

718362

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.213

AC:

32404

AN:

152126

Hom.:

3445

Cov.:

AF XY:

0.215

AC XY:

15992

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.195

Alfa

AF:

0.207

Hom.:

1083

Bravo

AF:

0.206

Asia WGS

AF:

0.179

AC:

628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.58

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