Genetic Variant NM_173662.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF175	NM_173662.4 link	c.510-33A>G		intron_variant	Intron 5 of 8	ENST00000347063.9	NP_775933.2	Q8N4F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF175	ENST00000347063.9 link	c.510-33A>G		intron_variant	Intron 5 of 8	1	NM_173662.4	ENSP00000340979.4		Q8N4F7-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over