NM_001039348.3:c.517+9973C>T

Variant names:

• chr2-55907692-G-A
• rs1430197
• NM_001039348.3:c.517+9973C>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.517+9973C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,042 control chromosomes in the GnomAD database, including 13,383 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 0.41 (13383 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 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.517+9973C>T		intron	N/A	NP_001034437.1
	EFEMP1	NM_001039349.3		c.517+9973C>T		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.517+9973C>T		intron	N/A	ENSP00000347596.3
	EFEMP1	ENST00000394555.6	TSL:1	c.517+9973C>T		intron	N/A	ENSP00000378058.2
	EFEMP1	ENST00000634374.1	TSL:5	c.115+9973C>T		intron	N/A	ENSP00000489183.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62606 AN: 151926 Hom.: 13371 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.412 AC: 62660 AN: 152042 Hom.: 13383 Cov.: 32 AF XY: 0.413 AC XY: 30679 AN XY: 74314

African (AFR) AF: 0.471 AC: 19555 AN: 41488

American (AMR) AF: 0.352 AC: 5370 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1315 AN: 3464

East Asian (EAS) AF: 0.744 AC: 3849 AN: 5172

South Asian (SAS) AF: 0.493 AC: 2379 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3181 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25543 AN: 67950

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.383 Hom.: 23823

Bravo AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.43
PhyloP100		-0.65
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: rs1430197; hg19: chr2-56134827;