rs659824

Positions:

• chr11-65869038-A-G
• chr11-65869038-A-T

Variant summary

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

The NM_016938.5(EFEMP2):​c.728-409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 294,360 control chromosomes in the GnomAD database, including 34,707 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 0.45 (16219 hom., cov: 32)
  • Exomes 𝑓: 0.50 (18488 hom.)
• Consequence: EFEMP2 NM_016938.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

EFEMP2 (HGNC:3219): (EGF containing fibulin extracellular matrix protein 2) A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implicated in functions as diverse as blood coagulation, activation of complement and determination of cell fate during development. The protein encoded by this gene contains four EGF2 domains and six calcium-binding EGF2 domains. This gene is necessary for elastic fiber formation and connective tissue development. Defects in this gene are cause of an autosomal recessive cutis laxa syndrome. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

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 (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFEMP2	NM_016938.5	c.728-409T>C		intron_variant		ENST00000307998.11
EFEMP2	NR_037718.2	n.853-409T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFEMP2	ENST00000307998.11	c.728-409T>C		intron_variant		1	NM_016938.5	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68471 AN: 151916 Hom.: 16222 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.499 AC: 71052 AN: 142326 Hom.: 18488 Cov.: 0 AF XY: 0.508 AC XY: 39150 AN XY: 77134

Gnomad4 AFR exome AF: 0.335

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.450 AC: 68490 AN: 152034 Hom.: 16219 Cov.: 32 AF XY: 0.453 AC XY: 33659 AN XY: 74302

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.484

Alfa AF: 0.482 Hom.: 5128

Bravo AF: 0.425

Asia WGS AF: 0.391 AC: 1359 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	4.1
DANN	Benign	0.78

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: rs659824; hg19: chr11-65636509;