2-55918406-T-C

Variant names:

• chr2-55918406-T-C
• rs2277887
• NM_001039348.3:c.82-139A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039348.3(EFEMP1):​c.82-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,015,658 control chromosomes in the GnomAD database, including 3,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (459 hom., cov: 32)
  • Exomes 𝑓: 0.074 (3037 hom.)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-55918406-T-C is Benign according to our data. Variant chr2-55918406-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.82-139A>G		intron_variant	Intron 3 of 11	ENST00000355426.8	NP_001034437.1
EFEMP1	NM_001039349.3	c.82-139A>G		intron_variant	Intron 2 of 10		NP_001034438.1
EFEMP1	XM_005264205.5	c.82-139A>G		intron_variant	Intron 3 of 9		XP_005264262.2
EFEMP1	XM_017003586.3	c.82-139A>G		intron_variant	Intron 2 of 8		XP_016859075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.82-139A>G		intron_variant	Intron 3 of 11	1	NM_001039348.3	ENSP00000347596.3

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10062 AN: 152122 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0865

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0722

Gnomad OTH AF: 0.0801

GnomAD4 exome AF: 0.0744 AC: 64222 AN: 863418 Hom.: 3037 AF XY: 0.0756 AC XY: 33942 AN XY: 448960

African (AFR) AF: 0.0286 AC: 618 AN: 21628

American (AMR) AF: 0.0717 AC: 2737 AN: 38184

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 937 AN: 21842

East Asian (EAS) AF: 0.214 AC: 7688 AN: 35928

South Asian (SAS) AF: 0.0910 AC: 6464 AN: 71010

European-Finnish (FIN) AF: 0.0710 AC: 3608 AN: 50846

Middle Eastern (MID) AF: 0.102 AC: 322 AN: 3164

European-Non Finnish (NFE) AF: 0.0671 AC: 38945 AN: 580498

Other (OTH) AF: 0.0720 AC: 2903 AN: 40318

GnomAD4 genome AF: 0.0661 AC: 10070 AN: 152240 Hom.: 459 Cov.: 32 AF XY: 0.0682 AC XY: 5079 AN XY: 74436

African (AFR) AF: 0.0308 AC: 1280 AN: 41554

American (AMR) AF: 0.0736 AC: 1126 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5168

South Asian (SAS) AF: 0.0866 AC: 417 AN: 4818

European-Finnish (FIN) AF: 0.0620 AC: 658 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0722 AC: 4912 AN: 68010

Other (OTH) AF: 0.0859 AC: 181 AN: 2108

Alfa AF: 0.0697 Hom.: 360

Bravo AF: 0.0680

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.9
DANN	Benign	0.71
PhyloP100		-0.12
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: rs2277887; hg19: chr2-56145541;