rs1430193

Variant names:

• chr2-55893718-A-T
• rs1430193
• NM_001039348.3:c.518-11984T>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.518-11984T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,050 control chromosomes in the GnomAD database, including 20,393 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 0.49 (20393 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 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.518-11984T>A		intron	N/A	NP_001034437.1	Q12805-1
	EFEMP1	NM_001039349.3		c.518-11984T>A		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.518-11984T>A		intron	N/A	ENSP00000347596.3	Q12805-1
	EFEMP1	ENST00000394555.6	TSL:1	c.518-11984T>A		intron	N/A	ENSP00000378058.2	Q12805-1
	EFEMP1	ENST00000881458.1		c.668-11984T>A		intron	N/A	ENSP00000551517.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73979 AN: 151932 Hom.: 20363 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.487 AC: 74057 AN: 152050 Hom.: 20393 Cov.: 32 AF XY: 0.491 AC XY: 36497 AN XY: 74320

African (AFR) AF: 0.712 AC: 29520 AN: 41488

American (AMR) AF: 0.407 AC: 6219 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4624 AN: 5180

South Asian (SAS) AF: 0.514 AC: 2478 AN: 4822

European-Finnish (FIN) AF: 0.367 AC: 3875 AN: 10568

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24347 AN: 67922

Other (OTH) AF: 0.499 AC: 1054 AN: 2114

Alfa AF: 0.419 Hom.: 1832

Bravo AF: 0.501

Asia WGS AF: 0.687 AC: 2389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.73
PhyloP100		-0.50
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: rs1430193; hg19: chr2-56120853;