Variant 2-55867066-GA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001039348.3(EFEMP1):c.*6del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,612,118 control chromosomes in the GnomAD database, including 958 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 54 hom., cov: 32)

Exomes 𝑓: 0.027 ( 904 hom. )

Consequence

EFEMP1
NM_001039348.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.340

Variant links:

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]

EFEMP1 links:

LOC112268416 (HGNC:):

LOC112268416 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-55867066-GA-G is Benign according to our data. Variant chr2-55867066-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 191301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-55867066-GA-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFEMP1	NM_001039348.3 linkuse as main transcript	c.*6del		3_prime_UTR_variant	12/12	ENST00000355426.8
LOC112268416	XR_002959388.2 linkuse as main transcript	n.229-6813del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFEMP1	ENST00000355426.8 linkuse as main transcript	c.*6del	3_prime_UTR_variant	12/12	1	NM_001039348.3	P1	Q12805-1
EFEMP1	ENST00000394555.6 linkuse as main transcript	c.*6del	3_prime_UTR_variant	11/11	1		P1	Q12805-1
EFEMP1	ENST00000634374.1 linkuse as main transcript	c.*6del	3_prime_UTR_variant	6/6	5
EFEMP1	ENST00000635671.1 linkuse as main transcript	c.*1140del	3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2973

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00459

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0675

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0816

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0243

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0290

AC:

7277

AN:

251226

Hom.:

233

AF XY:

0.0332

AC XY:

4507

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0703

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0842

Gnomad FIN exome

AF:

0.0158

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0268

AC:

39169

AN:

1459974

Hom.:

904

Cov.:

AF XY:

0.0291

AC XY:

21106

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.00362

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0689

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0865

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0305

GnomAD4 genome

AF:

0.0195

AC:

2972

AN:

152144

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1524

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00458

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.0675

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0817

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.0243

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0305

Hom.:

Bravo

AF:

0.0182

Asia WGS

AF:

0.0350

AC:

124

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	research	Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre	Sep 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 03, 2014	- -

Doyne honeycomb retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over