2-55883417-T-C

Position:

• chr2-55883417-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039348.3(EFEMP1):​c.518-1683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,068 control chromosomes in the GnomAD database, including 34,806 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 0.66 (34806 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.518-1683A>G		intron_variant		ENST00000355426.8	NP_001034437.1
EFEMP1	NM_001039349.3	c.518-1683A>G		intron_variant			NP_001034438.1
EFEMP1	XM_005264205.5	c.518-1683A>G		intron_variant			XP_005264262.2
EFEMP1	XM_017003586.3	c.518-1683A>G		intron_variant			XP_016859075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.518-1683A>G		intron_variant		1	NM_001039348.3	ENSP00000347596	P1
EFEMP1	ENST00000394555.6	c.518-1683A>G		intron_variant		1		ENSP00000378058	P1
EFEMP1	ENST00000634374.1	c.117-1683A>G		intron_variant		5		ENSP00000489183
EFEMP1	ENST00000635671.1	c.*410-1683A>G		intron_variant, NMD_transcript_variant		2		ENSP00000489578

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99580 AN: 151950 Hom.: 34761 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.656 AC: 99681 AN: 152068 Hom.: 34806 Cov.: 32 AF XY: 0.654 AC XY: 48589 AN XY: 74322

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.664

Alfa AF: 0.599 Hom.: 6492

Bravo AF: 0.667

Asia WGS AF: 0.792 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.82

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: rs3791676; hg19: chr2-56110552;