4-153713877-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173662.4(RNF175):c.765-1301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 152,312 control chromosomes in the GnomAD database, including 71,655 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 0.97 (71655 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RNF175 NM_173662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF175	NM_173662.4	c.765-1301A>G		intron_variant		ENST00000347063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF175	ENST00000347063.9	c.765-1301A>G		intron_variant		1	NM_173662.4	P1
RNF175	ENST00000503694.5	c.*1895A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2
RNF175	ENST00000513656.5	c.*512-1301A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147497 AN: 152194 Hom.: 71596 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.976

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

GnomAD4 genome AF: 0.969 AC: 147615 AN: 152312 Hom.: 71655 Cov.: 32 AF XY: 0.970 AC XY: 72280 AN XY: 74484

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.995

Gnomad4 OTH AF: 0.976

Alfa AF: 0.965 Hom.: 10669

Bravo AF: 0.965

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.0
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs6535946; hg19: chr4-154635029;