Genetic Variant EFEMP1:c.-48-328T>C (chr2-55923267-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039348.3(EFEMP1):c.-48-328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,028 control chromosomes in the GnomAD database, including 14,924 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 0.38 ( 14924 hom., cov: 32)

Consequence

EFEMP1
NM_001039348.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.77

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: 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3 link	c.-48-328T>C	intron_variant	Intron 1 of 11	ENST00000355426.8	NP_001034437.1	Q12805-1A0A0S2Z4F1B2R6M6
EFEMP1	NM_001039349.3 link	c.-8+444T>C	intron_variant	Intron 1 of 10		NP_001034438.1	Q12805-1A0A0S2Z4F1
EFEMP1	XM_005264205.5 link	c.-48-328T>C	intron_variant	Intron 1 of 9		XP_005264262.2	A0A0S2Z3V1
EFEMP1	XM_017003586.3 link	c.-8+444T>C	intron_variant	Intron 1 of 8		XP_016859075.1	A0A0S2Z3V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8 link	c.-48-328T>C		intron_variant	Intron 1 of 11	1	NM_001039348.3	ENSP00000347596.3		Q12805-1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58111

AN:

151910

Hom.:

14886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.0692

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.383

AC:

58199

AN:

152028

Hom.:

14924

Cov.:

AF XY:

0.379

AC XY:

28190

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.726

AC:

30090

AN:

41458

American (AMR)

AF:

0.283

AC:

4312

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1129

AN:

3462

East Asian (EAS)

AF:

0.0690

AC:

356

AN:

5158

South Asian (SAS)

AF:

0.503

AC:

2420

AN:

4814

European-Finnish (FIN)

AF:

0.197

AC:

2081

AN:

10590

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16763

AN:

67976

Other (OTH)

AF:

0.364

AC:

765

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1497

2993

4490

5986

7483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.297

Hom.:

12215

Bravo

AF:

0.395

Asia WGS

AF:

0.311

AC:

1082

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.11

(source)

DANN

Benign

0.65

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over