chr2-55885305-C-A

Variant names:

• chr2-55885305-C-A
• rs1367228
• NM_001039348.3:c.518-3571G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039348.3(EFEMP1):​c.518-3571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,014 control chromosomes in the GnomAD database, including 24,201 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 0.54 (24201 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 17 publications found

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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 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.518-3571G>T		intron	N/A	NP_001034437.1	Q12805-1
	EFEMP1	NM_001039349.3		c.518-3571G>T		intron	N/A	NP_001034438.1	Q12805-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFEMP1	ENST00000355426.8	TSL:1 MANE Select	c.518-3571G>T		intron	N/A	ENSP00000347596.3	Q12805-1
	EFEMP1	ENST00000394555.6	TSL:1	c.518-3571G>T		intron	N/A	ENSP00000378058.2	Q12805-1
	EFEMP1	ENST00000881458.1		c.668-3571G>T		intron	N/A	ENSP00000551517.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82558 AN: 151896 Hom.: 24168 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.544 AC: 82642 AN: 152014 Hom.: 24201 Cov.: 32 AF XY: 0.546 AC XY: 40601 AN XY: 74304

African (AFR) AF: 0.733 AC: 30421 AN: 41474

American (AMR) AF: 0.447 AC: 6836 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3468

East Asian (EAS) AF: 0.897 AC: 4632 AN: 5164

South Asian (SAS) AF: 0.656 AC: 3150 AN: 4804

European-Finnish (FIN) AF: 0.372 AC: 3929 AN: 10554

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29931 AN: 67948

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.494 Hom.: 40205

Bravo AF: 0.553

Asia WGS AF: 0.761 AC: 2648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.45
PhyloP100		0.064
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

Other links and lift over

dbSNP: rs1367228; hg19: chr2-56112440;