rs594689

chr11-65868088-G-Achr11-65868088-G-Cchr11-65868088-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.57

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 -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	UniProt
EFEMP2	NM_016938.5	c.975-32C>T		intron_variant		ENST00000307998.11
EFEMP2	NR_037718.2	n.1100-32C>T		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60183 AN: 151854 Hom.: 14046 Cov.: 31

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

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.: 34 AF XY: 0.496 AC XY: 358827 AN XY: 724120

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.: 31 AF XY: 0.401 AC XY: 29767 AN XY: 74278

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cutis laxa, autosomal recessive, type 1B Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs594689; hg19: chr11-65635559;