2-55871137-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039348.3(EFEMP1):c.1001-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 1,612,978 control chromosomes in the GnomAD database, including 3,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 269 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2828 hom. )

Consequence

EFEMP1
NM_001039348.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.26

Publications

7 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
open-angle glaucoma
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
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

new If you want to explore the variant's impact on the transcript NM_001039348.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-55871137-G-A is Benign according to our data. Variant chr2-55871137-G-A is described in ClinVar as Benign. ClinVar VariationId is 257227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039348.3. 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
	EFEMP1	NM_001039348.3	MANE Select	c.1001-14C>T		intron	N/A	NP_001034437.1	Q12805-1
	EFEMP1	NM_001039349.3		c.1001-14C>T		intron	N/A	NP_001034438.1	Q12805-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFEMP1	ENST00000355426.8	TSL:1 MANE Select	c.1001-14C>T	intron	N/A	ENSP00000347596.3	Q12805-1
EFEMP1	ENST00000394555.6	TSL:1	c.1001-14C>T	intron	N/A	ENSP00000378058.2	Q12805-1
EFEMP1	ENST00000881458.1		c.1151-14C>T	intron	N/A	ENSP00000551517.1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8349

AN:

152014

Hom.:

270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0272

Gnomad FIN

AF:

0.0633

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0653

Gnomad OTH

AF:

0.0794

GnomAD2 exomes

AF:

0.0527

AC:

13203

AN:

250506

AF XY:

0.0529

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0393

Gnomad ASJ exome

AF:

0.0791

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0638

Gnomad NFE exome

AF:

0.0680

Gnomad OTH exome

AF:

0.0587

GnomAD4 exome

AF:

0.0587

AC:

85788

AN:

1460846

Hom.:

2828

Cov.:

AF XY:

0.0583

AC XY:

42335

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.0389

AC:

1301

AN:

33438

American (AMR)

AF:

0.0411

AC:

1832

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

1985

AN:

26100

East Asian (EAS)

AF:

0.000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.0321

AC:

2764

AN:

86238

European-Finnish (FIN)

AF:

0.0640

AC:

3411

AN:

53332

Middle Eastern (MID)

AF:

0.0816

AC:

470

AN:

5762

European-Non Finnish (NFE)

AF:

0.0636

AC:

70627

AN:

1111332

Other (OTH)

AF:

0.0562

AC:

3388

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4241

8482

12723

16964

21205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2518

5036

7554

10072

12590

<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:

0.0549

AC:

8346

AN:

152132

Hom.:

269

Cov.:

AF XY:

0.0552

AC XY:

4102

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0394

AC:

1636

AN:

41510

American (AMR)

AF:

0.0608

AC:

928

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3470

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.0274

AC:

132

AN:

4820

European-Finnish (FIN)

AF:

0.0633

AC:

671

AN:

10592

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0653

AC:

4437

AN:

67992

Other (OTH)

AF:

0.0786

AC:

166

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

384

767

1151

1534

1918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0409

Hom.:

Bravo

AF:

0.0532

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Doyne honeycomb retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over