Genetic Variant MFAP2:p.His144His (chr1-16975285-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002403.4(MFAP2):c.432T>C(p.His144His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,612,558 control chromosomes in the GnomAD database, including 181,000 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 0.46 ( 15982 hom., cov: 31)

Exomes 𝑓: 0.47 ( 165018 hom. )

Consequence

MFAP2
NM_002403.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.372

Publications

40 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=-0.372 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP2	NM_002403.4 link	c.432T>C	p.His144His	synonymous_variant	Exon 8 of 9	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MFAP2	ENST00000375535.4 link	c.432T>C	p.His144His	synonymous_variant	Exon 8 of 9	1	NM_002403.4	ENSP00000364685.3
MFAP2	ENST00000375534.7 link	c.429T>C	p.His143His	synonymous_variant	Exon 7 of 8	2		ENSP00000364684.3
MFAP2	ENST00000490075.5 link	n.1833T>C		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69182

AN:

151840

Hom.:

15970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.475

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.463

GnomAD2 exomes

AF:

0.446

AC:

111373

AN:

249980

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.473

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.472

AC:

689661

AN:

1460600

Hom.:

165018

Cov.:

AF XY:

0.471

AC XY:

342134

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.454

AC:

15181

AN:

33452

American (AMR)

AF:

0.483

AC:

21539

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

12504

AN:

26066

East Asian (EAS)

AF:

0.273

AC:

10840

AN:

39692

South Asian (SAS)

AF:

0.444

AC:

38245

AN:

86122

European-Finnish (FIN)

AF:

0.387

AC:

20656

AN:

53384

Middle Eastern (MID)

AF:

0.462

AC:

2655

AN:

5750

European-Non Finnish (NFE)

AF:

0.486

AC:

540564

AN:

1111240

Other (OTH)

AF:

0.456

AC:

27477

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18766

37531

56297

75062

93828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15924

31848

47772

63696

79620

<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:

0.456

AC:

69217

AN:

151958

Hom.:

15982

Cov.:

AF XY:

0.449

AC XY:

33370

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.455

AC:

18838

AN:

41424

American (AMR)

AF:

0.460

AC:

7014

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

1648

AN:

3468

East Asian (EAS)

AF:

0.249

AC:

1285

AN:

5162

South Asian (SAS)

AF:

0.435

AC:

2095

AN:

4818

European-Finnish (FIN)

AF:

0.378

AC:

4001

AN:

10584

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32843

AN:

67930

Other (OTH)

AF:

0.458

AC:

963

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1974

3948

5922

7896

9870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.472

Hom.:

46709

Bravo

AF:

0.461

Asia WGS

AF:

0.330

AC:

1148

AN:

3478

EpiCase

AF:

0.479

EpiControl

AF:

0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.76

(source)

DANN

Benign

0.58

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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