rs1439166

Positions:

• chr4-153720337-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.510-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,593,066 control chromosomes in the GnomAD database, including 272,537 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 0.53 (22196 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250341 hom.)
• Consequence: RNF175 NM_173662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF175	NM_173662.4	c.510-33A>G		intron_variant		ENST00000347063.9	NP_775933.2
LOC105377499	XR_007058334.1	n.40T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF175	ENST00000347063.9	c.510-33A>G		intron_variant		1	NM_173662.4	ENSP00000340979	P1
	ENST00000505051.1	n.11T>C		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80771 AN: 151948 Hom.: 22189 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.528

GnomAD3 exomes AF: 0.516 AC: 127735 AN: 247518 Hom.: 35462 AF XY: 0.518 AC XY: 69503 AN XY: 134288

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.514

Gnomad EAS exome AF: 0.308

Gnomad SAS exome AF: 0.332

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.625

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.580 AC: 835883 AN: 1441000 Hom.: 250341 Cov.: 25 AF XY: 0.575 AC XY: 412471 AN XY: 717720

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.531 AC: 80797 AN: 152066 Hom.: 22196 Cov.: 32 AF XY: 0.525 AC XY: 39000 AN XY: 74348

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.523

Alfa AF: 0.592 Hom.: 49699

Bravo AF: 0.514

Asia WGS AF: 0.317 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.73

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: rs1439166; hg19: chr4-154641489; COSMIC: COSV56841053; COSMIC: COSV56841053;