rs2903838

chr2-55923267-A-G

Variant summary

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

The NM_001039348.3(EFEMP1):c.-48-328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,028 control chromosomes in the GnomAD database, including 14,924 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 0.38 (14924 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFEMP1	NM_001039348.3	c.-48-328T>C		intron_variant		ENST00000355426.8
EFEMP1	NM_001039349.3	c.-8+444T>C		intron_variant
EFEMP1	XM_005264205.5	c.-48-328T>C		intron_variant
EFEMP1	XM_017003586.3	c.-8+444T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFEMP1	ENST00000355426.8	c.-48-328T>C		intron_variant		1	NM_001039348.3	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58111 AN: 151910 Hom.: 14886 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.383 AC: 58199 AN: 152028 Hom.: 14924 Cov.: 32 AF XY: 0.379 AC XY: 28190 AN XY: 74312

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0690

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.364

Alfa AF: 0.312 Hom.: 2677

Bravo AF: 0.395

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.11
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2903838; hg19: chr2-56150402;