2-55867066-GAA-GA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001039348.3(EFEMP1):c.*6delT 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 U:1B:4

Conservation

PhyloP100: 0.340

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Doyne honeycomb retinal dystrophy
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet, G2P
cutis laxa, autosomal recessive, type 1d
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
cutis laxa
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

EFEMP1 links:

LOC112268416 (HGNC:):

LOC112268416 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 191301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3 link	c.*6delT		3_prime_UTR_variant	Exon 12 of 12	ENST00000355426.8	NP_001034437.1	Q12805-1A0A0S2Z4F1B2R6M6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8 link	c.*6delT		3_prime_UTR_variant	Exon 12 of 12	1	NM_001039348.3	ENSP00000347596.3		Q12805-1

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

GnomAD2 exomes

AF:

0.0290

AC:

7277

AN:

251226

AF XY:

0.0332

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 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

African (AFR)

AF:

0.00362

AC:

121

AN:

33428

American (AMR)

AF:

0.0124

AC:

553

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0689

AC:

1800

AN:

26126

East Asian (EAS)

AF:

0.000277

AC:

AN:

39684

South Asian (SAS)

AF:

0.0865

AC:

7452

AN:

86182

European-Finnish (FIN)

AF:

0.0173

AC:

925

AN:

53400

Middle Eastern (MID)

AF:

0.0837

AC:

372

AN:

4444

European-Non Finnish (NFE)

AF:

0.0235

AC:

26100

AN:

1111760

Other (OTH)

AF:

0.0305

AC:

1835

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2036

4072

6107

8143

10179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

982

1964

2946

3928

4910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0195

AC:

2972

AN:

152144

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1524

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00458

AC:

190

AN:

41530

American (AMR)

AF:

0.0130

AC:

198

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0675

AC:

234

AN:

3466

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0817

AC:

393

AN:

4810

European-Finnish (FIN)

AF:

0.0187

AC:

198

AN:

10596

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0243

AC:

1654

AN:

67984

Other (OTH)

AF:

0.0275

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

138

276

415

553

691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 28, 2016

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinal dystrophy

Uncertain:1

Jan 01, 2010

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Doyne honeycomb retinal dystrophy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over