4-153714284-C-G

Variant names:

• chr4-153714284-C-G
• rs7695605
• NM_173662.4:c.764+1245G>C

Variant summary

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

The ENST00000347063.9(RNF175):​c.764+1245G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,124 control chromosomes in the GnomAD database, including 4,004 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 0.23 (4004 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RNF175 ENST00000347063.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000347063.9. 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.764+1245G>C		intron	N/A	NP_775933.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF175	ENST00000347063.9	TSL:1 MANE Select	c.764+1245G>C		intron	N/A	ENSP00000340979.4
	RNF175	ENST00000503694.5	TSL:2	n.*1488G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000424430.1
	RNF175	ENST00000503694.5	TSL:2	n.*1488G>C		3_prime_UTR	Exon 6 of 6	ENSP00000424430.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34917 AN: 152006 Hom.: 4001 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.218

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.230 AC: 34929 AN: 152124 Hom.: 4004 Cov.: 32 AF XY: 0.232 AC XY: 17286 AN XY: 74372

African (AFR) AF: 0.200 AC: 8309 AN: 41504

American (AMR) AF: 0.250 AC: 3825 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1170 AN: 5172

South Asian (SAS) AF: 0.226 AC: 1091 AN: 4828

European-Finnish (FIN) AF: 0.273 AC: 2888 AN: 10574

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16081 AN: 67980

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.229 Hom.: 502

Bravo AF: 0.220

Asia WGS AF: 0.190 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.3
DANN	Benign	0.63
PhyloP100		0.52
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: rs7695605; hg19: chr4-154635436;