4-153743545-T-G

Variant names:

• chr4-153743545-T-G
• rs11099896
• NM_173662.4:c.246+5100A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.88).
• 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 rank	MANE	Protein	UniProt
RNF175	NM_173662.4	c.246+5100A>C		intron_variant	Intron 3 of 8	ENST00000347063.9	NP_775933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF175	ENST00000347063.9	c.246+5100A>C		intron_variant	Intron 3 of 8	1	NM_173662.4	ENSP00000340979.4

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

African (AFR) AF: 0.313 AC: 12954 AN: 41390

American (AMR) AF: 0.273 AC: 4160 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4184 AN: 5154

South Asian (SAS) AF: 0.336 AC: 1620 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3109 AN: 10538

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16718 AN: 67924

Other (OTH) AF: 0.283 AC: 595 AN: 2102

Alfa AF: 0.257 Hom.: 18972

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
PhyloP100		-0.94
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: rs11099896; hg19: chr4-154664697;