11-117286177-G-T

Position:

• chr11-117286177-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000300650.9(RNF214):​c.*1026G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 152,674 control chromosomes in the GnomAD database, including 6 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 0.0069 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: RNF214 ENST00000300650.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

Genes affected

BACE1 (HGNC:933): (beta-secretase 1) This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]

RNF214 (HGNC:25335): (ring finger protein 214) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACE1	NM_012104.6	c.*3389C>A		3_prime_UTR_variant	9/9	ENST00000313005.11	NP_036236.1
RNF214	NM_207343.4	c.*1026G>T		3_prime_UTR_variant	15/15	ENST00000300650.9	NP_997226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.*1026G>T		3_prime_UTR_variant	15/15	1	NM_207343.4	ENSP00000300650	P3
BACE1	ENST00000313005.11	c.*3389C>A		3_prime_UTR_variant	9/9	1	NM_012104.6	ENSP00000318585	P1

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1043 AN: 152122 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.00691 AC: 3 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.00769 AC XY: 2 AN XY: 260

Gnomad4 FIN exome AF: 0.00708

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00685 AC: 1043 AN: 152240 Hom.: 6 Cov.: 32 AF XY: 0.00627 AC XY: 467 AN XY: 74458

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.000326 Hom.: 125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
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: rs1047964; hg19: chr11-117156893;