NM_001039348.3:c.518-2440G>A

Variant names:

• chr2-55884174-C-T
• rs3791675
• NM_001039348.3:c.518-2440G>A

Variant summary

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

The NM_001039348.3(EFEMP1):​c.518-2440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,118 control chromosomes in the GnomAD database, including 4,818 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 0.21 (4818 hom., cov: 33)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 85 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.518-2440G>A		intron	N/A	NP_001034437.1
	EFEMP1	NM_001039349.3		c.518-2440G>A		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.518-2440G>A		intron	N/A	ENSP00000347596.3
	EFEMP1	ENST00000394555.6	TSL:1	c.518-2440G>A		intron	N/A	ENSP00000378058.2
	EFEMP1	ENST00000634374.1	TSL:5	c.116-2440G>A		intron	N/A	ENSP00000489183.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32693 AN: 152000 Hom.: 4824 Cov.: 33

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.215 AC: 32678 AN: 152118 Hom.: 4818 Cov.: 33 AF XY: 0.220 AC XY: 16336 AN XY: 74366

African (AFR) AF: 0.0679 AC: 2818 AN: 41530

American (AMR) AF: 0.221 AC: 3371 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3905 AN: 5164

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4814

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10566

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16983 AN: 67974

Other (OTH) AF: 0.243 AC: 514 AN: 2116

Alfa AF: 0.249 Hom.: 22344

Bravo AF: 0.211

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		-0.46
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: rs3791675; hg19: chr2-56111309;