2-55918406-T-C

Position:

• chr2-55918406-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000355426.8(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 ENST00000355426.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.82-139A>G		intron_variant		ENST00000355426.8	NP_001034437.1
EFEMP1	NM_001039349.3	c.82-139A>G		intron_variant			NP_001034438.1
EFEMP1	XM_005264205.5	c.82-139A>G		intron_variant			XP_005264262.2
EFEMP1	XM_017003586.3	c.82-139A>G		intron_variant			XP_016859075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.82-139A>G		intron_variant		1	NM_001039348.3	ENSP00000347596	P1

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

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.0429

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.0910

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.0671

Gnomad4 OTH exome AF: 0.0720

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

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.0736

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0722

Gnomad4 OTH AF: 0.0859

Alfa AF: 0.0703 Hom.: 213

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.9
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277887; hg19: chr2-56145541;