4-153710910-A-G

Position:

• chr4-153710910-A-G

Variant summary

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

The NM_173662.4(RNF175):​c.867-421T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,120 control chromosomes in the GnomAD database, including 6,933 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 (6933 hom., cov: 32)
• Consequence: RNF175 NM_173662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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 (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF175	NM_173662.4	c.867-421T>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.867-421T>C		intron_variant		1	NM_173662.4	ENSP00000340979	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43795 AN: 152002 Hom.: 6910 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.288 AC: 43841 AN: 152120 Hom.: 6933 Cov.: 32 AF XY: 0.294 AC XY: 21868 AN XY: 74374

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.286

Alfa AF: 0.322 Hom.: 1731

Bravo AF: 0.284

Asia WGS AF: 0.377 AC: 1309 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.015
DANN	Benign	0.44

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: rs11935252; hg19: chr4-154632062;