2-55867066-GAA-GA

Variant names:

• chr2-55867066-GA-G
• rs200536754
• NM_001039348.3:c.*6delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001039348.3(EFEMP1):​c.*6delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,612,118 control chromosomes in the GnomAD database, including 958 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (54 hom., cov: 32)
  • Exomes 𝑓: 0.027 (904 hom.)
• Consequence: EFEMP1 NM_001039348.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: 0.340
• 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: 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

LOC112268416 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-55867066-GA-G is Benign according to our data. Variant chr2-55867066-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 191301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.075 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.*6delT		3_prime_UTR	Exon 12 of 12	NP_001034437.1	Q12805-1
	EFEMP1	NM_001039349.3		c.*6delT		3_prime_UTR	Exon 11 of 11	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.*6delT		3_prime_UTR	Exon 12 of 12	ENSP00000347596.3	Q12805-1
	EFEMP1	ENST00000394555.6	TSL:1	c.*6delT		3_prime_UTR	Exon 11 of 11	ENSP00000378058.2	Q12805-1
	EFEMP1	ENST00000881458.1		c.*6delT		3_prime_UTR	Exon 12 of 12	ENSP00000551517.1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2973 AN: 152026 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0290 AC: 7277 AN: 251226 AF XY: 0.0332

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0703

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0359

GnomAD4 exome AF: 0.0268 AC: 39169 AN: 1459974 Hom.: 904 Cov.: 30 AF XY: 0.0291 AC XY: 21106 AN XY: 726300

African (AFR) AF: 0.00362 AC: 121 AN: 33428

American (AMR) AF: 0.0124 AC: 553 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 1800 AN: 26126

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39684

South Asian (SAS) AF: 0.0865 AC: 7452 AN: 86182

European-Finnish (FIN) AF: 0.0173 AC: 925 AN: 53400

Middle Eastern (MID) AF: 0.0837 AC: 372 AN: 4444

European-Non Finnish (NFE) AF: 0.0235 AC: 26100 AN: 1111760

Other (OTH) AF: 0.0305 AC: 1835 AN: 60234

GnomAD4 genome AF: 0.0195 AC: 2972 AN: 152144 Hom.: 54 Cov.: 32 AF XY: 0.0205 AC XY: 1524 AN XY: 74400

African (AFR) AF: 0.00458 AC: 190 AN: 41530

American (AMR) AF: 0.0130 AC: 198 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3466

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0817 AC: 393 AN: 4810

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1654 AN: 67984

Other (OTH) AF: 0.0275 AC: 58 AN: 2108

Alfa AF: 0.0305 Hom.: 15

Bravo AF: 0.0182

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Doyne honeycomb retinal dystrophy (1)
-	-	1	not provided (1)
-	1	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
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: rs200536754; hg19: chr2-56094201; COSMIC: COSV62614759;