Variant rs594689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016938.5(EFEMP2):c.975-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,608,318 control chromosomes in the GnomAD database, including 195,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14043 hom., cov: 31)

Exomes 𝑓: 0.49 ( 181043 hom. )

Consequence

EFEMP2
NM_016938.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.57

Variant links:

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]

EFEMP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-65868088-G-A is Benign according to our data. Variant chr11-65868088-G-A is described in ClinVar as [Benign]. Clinvar id is 1255373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFEMP2	NM_016938.5 linkuse as main transcript	c.975-32C>T		intron_variant		ENST00000307998.11	NP_058634.4
EFEMP2	NR_037718.2 linkuse as main transcript	n.1100-32C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFEMP2	ENST00000307998.11 linkuse as main transcript	c.975-32C>T		intron_variant		1	NM_016938.5	ENSP00000309953	P1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60183

AN:

151854

Hom.:

14046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.357

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.434

GnomAD3 exomes

AF:

0.448

AC:

108905

AN:

243216

Hom.:

26699

AF XY:

0.468

AC XY:

61786

AN XY:

131962

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.569

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.490

AC:

714066

AN:

1456346

Hom.:

181043

Cov.:

AF XY:

0.496

AC XY:

358827

AN XY:

724120

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.566

Gnomad4 FIN exome

AF:

0.564

Gnomad4 NFE exome

AF:

0.510

Gnomad4 OTH exome

AF:

0.471

GnomAD4 genome

AF:

0.396

AC:

60180

AN:

151972

Hom.:

14043

Cov.:

AF XY:

0.401

AC XY:

29767

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.357

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.545

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.518

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.448

Hom.:

4194

Bravo

AF:

0.363

Asia WGS

AF:

0.379

AC:

1320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Cutis laxa, autosomal recessive, type 1B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.9

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over