8-42856463-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030954.4(RNF170):c.508-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,427,078 control chromosomes in the GnomAD database, including 8,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1973 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6281 hom.)
• Consequence: RNF170 NM_030954.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

Genes affected

RNF170 (HGNC:25358): (ring finger protein 170) This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-42856463-A-G is Benign according to our data. Variant chr8-42856463-A-G is described in ClinVar as [Benign]. Clinvar id is 1244341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF170	NM_030954.4	c.508-35T>C		intron_variant		ENST00000527424.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF170	ENST00000527424.6	c.508-35T>C		intron_variant		1	NM_030954.4	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20536 AN: 151982 Hom.: 1961 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0967 AC: 23179 AN: 239660 Hom.: 1579 AF XY: 0.0955 AC XY: 12439 AN XY: 130230

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0665

Gnomad ASJ exome AF: 0.0348

Gnomad EAS exome AF: 0.000614

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.0928

Gnomad OTH exome AF: 0.0817

GnomAD4 exome AF: 0.0913 AC: 116444 AN: 1274978 Hom.: 6281 Cov.: 18 AF XY: 0.0910 AC XY: 58589 AN XY: 643826

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.0689

Gnomad4 ASJ exome AF: 0.0363

Gnomad4 EAS exome AF: 0.000542

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0939

GnomAD4 genome AF: 0.135 AC: 20590 AN: 152100 Hom.: 1973 Cov.: 32 AF XY: 0.136 AC XY: 10114 AN XY: 74364

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0692

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0994

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0906 Hom.: 774

Bravo AF: 0.135

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7014595; hg19: chr8-42711606;