chr4-153743545-T-G

Position:

• chr4-153743545-T-G

Variant summary

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

The NM_173662.4(RNF175):​c.246+5100A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,856 control chromosomes in the GnomAD database, including 7,224 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 0.29 (7224 hom., cov: 31)
• Consequence: RNF175 NM_173662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF175	NM_173662.4	c.246+5100A>C		intron_variant		ENST00000347063.9	NP_775933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF175	ENST00000347063.9	c.246+5100A>C		intron_variant		1	NM_173662.4	ENSP00000340979	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44131 AN: 151738 Hom.: 7222 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44136 AN: 151856 Hom.: 7224 Cov.: 31 AF XY: 0.297 AC XY: 22002 AN XY: 74202

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.283

Alfa AF: 0.238 Hom.: 6024

Bravo AF: 0.291

Asia WGS AF: 0.513 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.67

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: rs11099896; hg19: chr4-154664697;