11-117286177-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207343.4(RNF214):​c.*1026G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,664 control chromosomes in the GnomAD database, including 222 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 0.053 (219 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF214	NM_207343.4	c.*1026G>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000300650.9	NP_997226.2
BACE1	NM_012104.6	c.*3389C>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000313005.11	NP_036236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF214	ENST00000300650.9	c.*1026G>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_207343.4	ENSP00000300650.4
BACE1	ENST00000313005.11	c.*3389C>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_012104.6	ENSP00000318585.6

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8077 AN: 152112 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0945 AC: 41 AN: 434 Hom.: 3 Cov.: 0 AF XY: 0.0923 AC XY: 24 AN XY: 260

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: 0.0896 AC: 38 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.0531 AC: 8077 AN: 152230 Hom.: 219 Cov.: 32 AF XY: 0.0533 AC XY: 3969 AN XY: 74454

African (AFR) AF: 0.0567 AC: 2356 AN: 41532

American (AMR) AF: 0.0446 AC: 682 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 222 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5186

South Asian (SAS) AF: 0.0518 AC: 250 AN: 4824

European-Finnish (FIN) AF: 0.0748 AC: 793 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0518 AC: 3524 AN: 67998

Other (OTH) AF: 0.0624 AC: 132 AN: 2116

Alfa AF: 0.0442 Hom.: 125

Bravo AF: 0.0517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.74
DANN	Benign	0.74
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;