Variant 1-16974951-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002403.4(MFAP2):c.521C>G(p.Ala174Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 17)

Exomes 𝑓: 0.0053 ( 12 hom. )

Consequence

MFAP2
NM_002403.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

MFAP2 (HGNC:7033): (microfibril associated protein 2) Microfibrillar-associated protein 2 is a major antigen of elastin-associated microfibrils and a candidate for involvement in the etiology of inherited connective tissue diseases. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

MFAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025643706).

BP6

Variant 1-16974951-G-C is Benign according to our data. Variant chr1-16974951-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638387.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-16974951-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP2	NM_002403.4 linkuse as main transcript	c.521C>G	p.Ala174Gly	missense_variant	9/9	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4 linkuse as main transcript	c.521C>G	p.Ala174Gly	missense_variant	9/9	1	NM_002403.4	ENSP00000364685	A1	P55001-1
MFAP2	ENST00000375534.7 linkuse as main transcript	c.518C>G	p.Ala173Gly	missense_variant	8/8	2		ENSP00000364684	P4	P55001-2
MFAP2	ENST00000490075.5 linkuse as main transcript	n.1922C>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

584

AN:

143204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00397

Gnomad ASJ

AF:

0.000886

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00142

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00420

GnomAD3 exomes

AF:

0.00362

AC:

509

AN:

140732

Hom.:

AF XY:

0.00375

AC XY:

281

AN XY:

74920

show subpopulations

Gnomad AFR exome

AF:

0.000697

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.0000892

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00534

AC:

4467

AN:

835936

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

2284

AN XY:

429274

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00693

Gnomad4 OTH exome

AF:

0.00395

GnomAD4 genome

AF:

0.00407

AC:

584

AN:

143314

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

283

AN XY:

69344

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00397

Gnomad4 ASJ

AF:

0.000886

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00142

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00416

Alfa

AF:

0.00248

Hom.:

ExAC

AF:

0.00105

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MFAP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

.;N

MutationTaster

Benign

0.68

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.041

Sift

Benign

0.065

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0030

.;B

Vest4

0.13

MVP

0.10

MPC

0.49

ClinPred

0.0086

GERP RS

3.0

Varity_R

0.070

gMVP

0.25

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