2-55869757-A-G

Variant names:

• chr2-55869757-A-G
• rs3791679
• NM_001039348.3:c.1320+963T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001039348.3(EFEMP1):​c.1320+963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,166 control chromosomes in the GnomAD database, including 4,619 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 (4619 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 96 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.1320+963T>C		intron_variant	Intron 11 of 11	ENST00000355426.8	NP_001034437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.1320+963T>C		intron_variant	Intron 11 of 11	1	NM_001039348.3	ENSP00000347596.3
EFEMP1	ENST00000394555.6	c.1320+963T>C		intron_variant	Intron 10 of 10	1		ENSP00000378058.2
EFEMP1	ENST00000634374.1	c.678+963T>C		intron_variant	Intron 5 of 5	5		ENSP00000489183.1
EFEMP1	ENST00000635671.1	n.*972+963T>C		intron_variant	Intron 8 of 8	2		ENSP00000489578.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31782 AN: 152048 Hom.: 4624 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.209 AC: 31770 AN: 152166 Hom.: 4619 Cov.: 32 AF XY: 0.214 AC XY: 15919 AN XY: 74388

African (AFR) AF: 0.0653 AC: 2713 AN: 41564

American (AMR) AF: 0.217 AC: 3314 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3909 AN: 5152

South Asian (SAS) AF: 0.275 AC: 1328 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2395 AN: 10578

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16309 AN: 67986

Other (OTH) AF: 0.236 AC: 498 AN: 2112

Alfa AF: 0.241 Hom.: 23194

Bravo AF: 0.205

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		2.1
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: rs3791679; hg19: chr2-56096892;