Genetic Variant RNF175:c.510-33A>G (chr4-153720337-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173662.4(RNF175):c.510-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,593,066 control chromosomes in the GnomAD database, including 272,537 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 0.53 ( 22196 hom., cov: 32)

Exomes 𝑓: 0.58 ( 250341 hom. )

Consequence

RNF175
NM_173662.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

Publications

12 publications found

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:

ENSG00000249309 (HGNC:):

ENSG00000249309 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173662.4. 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
	RNF175	NM_173662.4	MANE Select	c.510-33A>G		intron	N/A	NP_775933.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNF175	ENST00000347063.9	TSL:1 MANE Select	c.510-33A>G	intron	N/A	ENSP00000340979.4
ENSG00000249309	ENST00000505051.1	TSL:3	n.11T>C	non_coding_transcript_exon	Exon 1 of 5
RNF175	ENST00000508248.1	TSL:5	c.330-33A>G	intron	N/A	ENSP00000427472.1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80771

AN:

151948

Hom.:

22189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.528

GnomAD2 exomes

AF:

0.516

AC:

127735

AN:

247518

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.580

AC:

835883

AN:

1441000

Hom.:

250341

Cov.:

AF XY:

0.575

AC XY:

412471

AN XY:

717720

show subpopulations

African (AFR)

AF:

0.428

AC:

14161

AN:

33106

American (AMR)

AF:

0.389

AC:

17294

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

13443

AN:

25904

East Asian (EAS)

AF:

0.279

AC:

11053

AN:

39564

South Asian (SAS)

AF:

0.337

AC:

28779

AN:

85448

European-Finnish (FIN)

AF:

0.648

AC:

34516

AN:

53240

Middle Eastern (MID)

AF:

0.502

AC:

2877

AN:

5734

European-Non Finnish (NFE)

AF:

0.622

AC:

680628

AN:

1093964

Other (OTH)

AF:

0.556

AC:

33132

AN:

59602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14250

28500

42750

57000

71250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17804

35608

53412

71216

89020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.531

AC:

80797

AN:

152066

Hom.:

22196

Cov.:

AF XY:

0.525

AC XY:

39000

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.437

AC:

18140

AN:

41464

American (AMR)

AF:

0.454

AC:

6938

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

1831

AN:

3472

East Asian (EAS)

AF:

0.311

AC:

1615

AN:

5186

South Asian (SAS)

AF:

0.329

AC:

1586

AN:

4824

European-Finnish (FIN)

AF:

0.657

AC:

6939

AN:

10566

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42032

AN:

67958

Other (OTH)

AF:

0.523

AC:

1105

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1852

3704

5557

7409

9261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.584

Hom.:

72084

Bravo

AF:

0.514

Asia WGS

AF:

0.317

AC:

1107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.60

(source)

DANN

Benign

0.73

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over