rs1346786

Positions:

• chr2-55881198-C-T

Variant summary

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

The NM_001039348.3(EFEMP1):​c.640+414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,010 control chromosomes in the GnomAD database, including 11,140 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 0.37 (11140 hom., cov: 32)
• Consequence: EFEMP1 NM_001039348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFEMP1	NM_001039348.3	c.640+414G>A		intron_variant		ENST00000355426.8	NP_001034437.1
EFEMP1	NM_001039349.3	c.640+414G>A		intron_variant			NP_001034438.1
EFEMP1	XM_005264205.5	c.640+414G>A		intron_variant			XP_005264262.2
EFEMP1	XM_017003586.3	c.640+414G>A		intron_variant			XP_016859075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFEMP1	ENST00000355426.8	c.640+414G>A		intron_variant		1	NM_001039348.3	ENSP00000347596	P1
EFEMP1	ENST00000394555.6	c.640+414G>A		intron_variant		1		ENSP00000378058	P1
EFEMP1	ENST00000634374.1	c.239+414G>A		intron_variant		5		ENSP00000489183
EFEMP1	ENST00000635671.1	c.*532+414G>A		intron_variant, NMD_transcript_variant		2		ENSP00000489578

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55870 AN: 151892 Hom.: 11125 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.368 AC: 55931 AN: 152010 Hom.: 11140 Cov.: 32 AF XY: 0.371 AC XY: 27604 AN XY: 74308

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.397

Alfa AF: 0.322 Hom.: 7844

Bravo AF: 0.373

Asia WGS AF: 0.565 AC: 1963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.64

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: rs1346786; hg19: chr2-56108333;