17-76216301-C-T

Position:

• chr17-76216301-C-T

Variant summary

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

The NM_052916.3(RNF157):​c.89-3819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,028 control chromosomes in the GnomAD database, including 2,269 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 0.14 (2269 hom., cov: 32)
• Consequence: RNF157 NM_052916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

Genes affected

RNF157 (HGNC:29402): (ring finger protein 157) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including negative regulation of signal transduction; positive regulation of dendrite extension; and protein autoubiquitination. Predicted to be located in cell body. Predicted to be active in early endosome; nucleus; and plasma 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF157	NM_052916.3	c.89-3819G>A		intron_variant		ENST00000269391.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF157	ENST00000269391.11	c.89-3819G>A		intron_variant		1	NM_052916.3	P4
RNF157	ENST00000319945.10	c.89-3819G>A		intron_variant		2
RNF157	ENST00000592271.1	c.89-3819G>A		intron_variant		2
RNF157	ENST00000647930.1	c.89-3819G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21447 AN: 151910 Hom.: 2260 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.141 AC: 21486 AN: 152028 Hom.: 2269 Cov.: 32 AF XY: 0.140 AC XY: 10398 AN XY: 74332

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0509

Gnomad4 NFE AF: 0.0758

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0881 Hom.: 1544

Bravo AF: 0.156

Asia WGS AF: 0.0670 AC: 235 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	0.95
DANN	Benign	0.72

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: rs10512605; hg19: chr17-74212382;