2-55866069-G-C

Variant names:

• chr2-55866069-G-C
• rs1802575
• NM_001039348.3:c.*1004C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039348.3(EFEMP1):​c.*1004C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,182 control chromosomes in the GnomAD database, including 726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (726 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EFEMP1 NM_001039348.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.571

Genes affected

EFEMP1 (HGNC:3218): (EGF containing fibulin extracellular matrix protein 1) This gene encodes a member of the fibulin family of extracellular matrix glycoproteins. Like all members of this family, the encoded protein contains tandemly repeated epidermal growth factor-like repeats followed by a C-terminus fibulin-type domain. This gene is upregulated in malignant gliomas and may play a role in the aggressive nature of these tumors. Mutations in this gene are associated with Doyne honeycomb retinal dystrophy. Alternatively spliced transcript variants that encode the same protein have been described.[provided by RefSeq, Nov 2009]

LOC112268416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-55866069-G-C is Benign according to our data. Variant chr2-55866069-G-C is described in ClinVar as [Benign]. Clinvar id is 336608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.*1004C>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000355426.8	NP_001034437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426	c.*1004C>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_001039348.3	ENSP00000347596.3
EFEMP1	ENST00000394555	c.*1004C>G		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000378058.2

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12609 AN: 152064 Hom.: 726 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0919

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AC: 0 AN: 0

Gnomad4 NFE exome AC: 0 AN: 0

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.0829 AC: 12609 AN: 152182 Hom.: 726 Cov.: 32 AF XY: 0.0795 AC XY: 5917 AN XY: 74410

Gnomad4 AFR AF: 0.0253 AC: 0.0253262 AN: 0.0253262

Gnomad4 AMR AF: 0.0764 AC: 0.0763689 AN: 0.0763689

Gnomad4 ASJ AF: 0.196 AC: 0.195502 AN: 0.195502

Gnomad4 EAS AF: 0.00424 AC: 0.00424056 AN: 0.00424056

Gnomad4 SAS AF: 0.0471 AC: 0.0470954 AN: 0.0470954

Gnomad4 FIN AF: 0.0754 AC: 0.0753541 AN: 0.0753541

Gnomad4 NFE AF: 0.122 AC: 0.121878 AN: 0.121878

Gnomad4 OTH AF: 0.0904 AC: 0.0904356 AN: 0.0904356

Alfa AF: 0.0911 Hom.: 91

Bravo AF: 0.0814

Asia WGS AF: 0.0230 AC: 81 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Doyne honeycomb retinal dystrophy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs1802575; hg19: chr2-56093204;