11-117286177-G-T

Variant names:

• chr11-117286177-G-T
• rs1047964
• NM_207343.4:c.*1026G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_207343.4(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 NM_207343.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 17 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF214	NM_207343.4	MANE Select	c.*1026G>T		3_prime_UTR	Exon 15 of 15	NP_997226.2	Q8ND24-1
	BACE1	NM_012104.6	MANE Select	c.*3389C>A		3_prime_UTR	Exon 9 of 9	NP_036236.1	P56817-1
	RNF214	NM_001077239.2		c.*1026G>T		3_prime_UTR	Exon 15 of 15	NP_001070707.1	Q8ND24-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF214	ENST00000300650.9	TSL:1 MANE Select	c.*1026G>T		3_prime_UTR	Exon 15 of 15	ENSP00000300650.4	Q8ND24-1
	BACE1	ENST00000313005.11	TSL:1 MANE Select	c.*3389C>A		3_prime_UTR	Exon 9 of 9	ENSP00000318585.6	P56817-1
	BACE1	ENST00000392937.10	TSL:1	c.*3389C>A		3_prime_UTR	Exon 8 of 8	ENSP00000475405.1	P56817-5

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00708 AC: 3 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 6

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000096912), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00197 AC: 82 AN: 41536

American (AMR) AF: 0.00490 AC: 75 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 728 AN: 68000

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.000326 Hom.: 125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

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: rs1047964; hg19: chr11-117156893;