2-55869757-A-G

Position:

• chr2-55869757-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC112268416 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.1320+963T>C		intron_variant		ENST00000355426.8	NP_001034437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.1320+963T>C		intron_variant		1	NM_001039348.3	ENSP00000347596.3
EFEMP1	ENST00000394555.6	c.1320+963T>C		intron_variant		1		ENSP00000378058.2
EFEMP1	ENST00000634374.1	c.678+963T>C		intron_variant		5		ENSP00000489183.1
EFEMP1	ENST00000635671.1	n.*972+963T>C		intron_variant		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

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.236

Alfa AF: 0.250 Hom.: 11857

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

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: rs3791679; hg19: chr2-56096892;