NM_001039348.3:c.518-1683A>G

Variant names:

• chr2-55883417-T-C
• rs3791676
• NM_001039348.3:c.518-1683A>G

Variant summary

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

The NM_001039348.3(EFEMP1):​c.518-1683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,068 control chromosomes in the GnomAD database, including 34,806 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 0.66 (34806 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 6 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFEMP1	NM_001039348.3	MANE Select	c.518-1683A>G		intron	N/A	NP_001034437.1
	EFEMP1	NM_001039349.3		c.518-1683A>G		intron	N/A	NP_001034438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFEMP1	ENST00000355426.8	TSL:1 MANE Select	c.518-1683A>G		intron	N/A	ENSP00000347596.3
	EFEMP1	ENST00000394555.6	TSL:1	c.518-1683A>G		intron	N/A	ENSP00000378058.2
	EFEMP1	ENST00000634374.1	TSL:5	c.116-1683A>G		intron	N/A	ENSP00000489183.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99580 AN: 151950 Hom.: 34761 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.656 AC: 99681 AN: 152068 Hom.: 34806 Cov.: 32 AF XY: 0.654 AC XY: 48589 AN XY: 74322

African (AFR) AF: 0.886 AC: 36799 AN: 41512

American (AMR) AF: 0.532 AC: 8119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3468

East Asian (EAS) AF: 0.899 AC: 4660 AN: 5184

South Asian (SAS) AF: 0.707 AC: 3401 AN: 4812

European-Finnish (FIN) AF: 0.447 AC: 4722 AN: 10552

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37397 AN: 67958

Other (OTH) AF: 0.664 AC: 1399 AN: 2106

Alfa AF: 0.598 Hom.: 39900

Bravo AF: 0.667

Asia WGS AF: 0.792 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		0.96
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: rs3791676; hg19: chr2-56110552;