rs960993

chr2-55909093-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.517+8572A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,026 control chromosomes in the GnomAD database, including 8,318 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 0.30 (8318 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFEMP1	NM_001039348.3	c.517+8572A>G		intron_variant		ENST00000355426.8
EFEMP1	NM_001039349.3	c.517+8572A>G		intron_variant
EFEMP1	XM_005264205.5	c.517+8572A>G		intron_variant
EFEMP1	XM_017003586.3	c.517+8572A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFEMP1	ENST00000355426.8	c.517+8572A>G		intron_variant		1	NM_001039348.3	P1
EFEMP1	ENST00000394555.6	c.517+8572A>G		intron_variant		1		P1
EFEMP1	ENST00000634374.1	c.116+8572A>G		intron_variant		5
EFEMP1	ENST00000635671.1	c.*409+8572A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45177 AN: 151908 Hom.: 8306 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.297 AC: 45224 AN: 152026 Hom.: 8318 Cov.: 32 AF XY: 0.294 AC XY: 21821 AN XY: 74318

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.298

Alfa AF: 0.255 Hom.: 731

Bravo AF: 0.307

Asia WGS AF: 0.200 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.37

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: rs960993; hg19: chr2-56136228;