Genetic Variant MFAP2:c.127+15G>A (chr1-16977094-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002403.4(MFAP2):c.127+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,088 control chromosomes in the GnomAD database, including 263,794 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 0.48 ( 18809 hom., cov: 32)

Exomes 𝑓: 0.57 ( 244985 hom. )

Consequence

MFAP2
NM_002403.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

16 publications found

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:

ENSG00000286898 (HGNC:):

ENSG00000286898 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP2	NM_002403.4 link	c.127+15G>A		intron_variant	Intron 3 of 8	ENST00000375535.4	NP_002394.1	P55001-1A0A024RA94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4 link	c.127+15G>A		intron_variant	Intron 3 of 8	1	NM_002403.4	ENSP00000364685.3		P55001-1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72256

AN:

151800

Hom.:

18806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.499

GnomAD2 exomes

AF:

0.515

AC:

128742

AN:

249902

AF XY:

0.521

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.605

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.592

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.573

AC:

836681

AN:

1461170

Hom.:

244985

Cov.:

AF XY:

0.571

AC XY:

414948

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.263

AC:

8819

AN:

33474

American (AMR)

AF:

0.520

AC:

23217

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

15997

AN:

26122

East Asian (EAS)

AF:

0.278

AC:

11015

AN:

39674

South Asian (SAS)

AF:

0.493

AC:

42481

AN:

86232

European-Finnish (FIN)

AF:

0.500

AC:

26602

AN:

53182

Middle Eastern (MID)

AF:

0.570

AC:

3285

AN:

5768

European-Non Finnish (NFE)

AF:

0.605

AC:

672568

AN:

1111722

Other (OTH)

AF:

0.542

AC:

32697

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

20375

40750

61125

81500

101875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18096

36192

54288

72384

90480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.476

AC:

72265

AN:

151918

Hom.:

18809

Cov.:

AF XY:

0.469

AC XY:

34866

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.277

AC:

11463

AN:

41426

American (AMR)

AF:

0.504

AC:

7703

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2126

AN:

3470

East Asian (EAS)

AF:

0.251

AC:

1286

AN:

5130

South Asian (SAS)

AF:

0.471

AC:

2264

AN:

4808

European-Finnish (FIN)

AF:

0.484

AC:

5121

AN:

10572

Middle Eastern (MID)

AF:

0.514

AC:

150

AN:

292

European-Non Finnish (NFE)

AF:

0.598

AC:

40618

AN:

67908

Other (OTH)

AF:

0.493

AC:

1042

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1786

3573

5359

7146

8932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.546

Hom.:

37712

Bravo

AF:

0.469

Asia WGS

AF:

0.337

AC:

1171

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

0.92

(source)

DANN

Benign

0.71

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over