NM_001039348.3:c.1001-14C>G

Variant names:

• chr2-55871137-G-C
• rs45535043
• NM_001039348.3:c.1001-14C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039348.3(EFEMP1):​c.1001-14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 7 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

LOC112268416 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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.1001-14C>G		intron	N/A	NP_001034437.1
	EFEMP1	NM_001039349.3		c.1001-14C>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.1001-14C>G		intron	N/A	ENSP00000347596.3
	EFEMP1	ENST00000394555.6	TSL:1	c.1001-14C>G		intron	N/A	ENSP00000378058.2
	EFEMP1	ENST00000634374.1	TSL:5	c.359-14C>G		intron	N/A	ENSP00000489183.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 36

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs45535043; hg19: chr2-56098272;