Variant rs753862645 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007046.4(EMILIN1):c.64G>A(p.Ala22Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,603,660 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

EMILIN1
NM_007046.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

EMILIN1 (HGNC:19880): (elastin microfibril interfacer 1) This gene encodes an extracellular matrix glycoprotein that is characterized by an N-terminal microfibril interface domain, a coiled-coiled alpha-helical domain, a collagenous domain and a C-terminal globular C1q domain. The encoded protein associates with elastic fibers at the interface between elastin and microfibrils and may play a role in the development of elastic tissues including large blood vessels, dermis, heart and lung. [provided by RefSeq, Sep 2009]

EMILIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN1	NM_007046.4 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	1/8	ENST00000380320.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN1	ENST00000380320.9 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	1/8	1	NM_007046.4	P1	Q9Y6C2-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000262

AC:

AN:

228902

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126808

show subpopulations

Gnomad AFR exome

AF:

0.0000770

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000993

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000896

AC:

AN:

1451416

Hom.:

Cov.:

AF XY:

0.00000969

AC XY:

AN XY:

722178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.0000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, autosomal dominant 10

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 17, 2023

- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2013

There is insufficient or conflicting evidence for classification of this alteration. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.80

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.36

REVEL

Benign

0.24

Sift

Uncertain

0.026

Sift4G

Benign

0.41

Polyphen

0.25

Vest4

0.81

MutPred

0.21

Gain of glycosylation at A22 (P = 0.0012);

MVP

0.61

MPC

0.72

ClinPred

0.070

GERP RS

4.4

Varity_R

0.048

gMVP

0.44

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

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