Genetic Variant MFAP2:c.448+92A>G (chr1-16975177-T-C) – 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.448+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,307,838 control chromosomes in the GnomAD database, including 119,310 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 0.41 ( 13204 hom., cov: 31)

Exomes 𝑓: 0.42 ( 106106 hom. )

Consequence

MFAP2
NM_002403.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

Publications

26 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MFAP2	NM_002403.4	MANE Select	c.448+92A>G	intron	N/A	NP_002394.1
MFAP2	NM_017459.3		c.448+92A>G	intron	N/A	NP_059453.1
MFAP2	NM_001135247.2		c.445+92A>G	intron	N/A	NP_001128719.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MFAP2	ENST00000375535.4	TSL:1 MANE Select	c.448+92A>G	intron	N/A	ENSP00000364685.3
MFAP2	ENST00000375534.7	TSL:2	c.445+92A>G	intron	N/A	ENSP00000364684.3
MFAP2	ENST00000490075.5	TSL:2	n.1849+92A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62666

AN:

151866

Hom.:

13195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.424

AC:

490102

AN:

1155854

Hom.:

106106

Cov.:

AF XY:

0.424

AC XY:

246247

AN XY:

580638

show subpopulations

African (AFR)

AF:

0.366

AC:

10178

AN:

27832

American (AMR)

AF:

0.461

AC:

17481

AN:

37882

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

9703

AN:

22038

East Asian (EAS)

AF:

0.271

AC:

10151

AN:

37432

South Asian (SAS)

AF:

0.416

AC:

30755

AN:

73898

European-Finnish (FIN)

AF:

0.361

AC:

18329

AN:

50744

Middle Eastern (MID)

AF:

0.431

AC:

2201

AN:

5106

European-Non Finnish (NFE)

AF:

0.436

AC:

370773

AN:

850900

Other (OTH)

AF:

0.410

AC:

20531

AN:

50022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

14116

28232

42349

56465

70581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10270

20540

30810

41080

51350

<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:

0.412

AC:

62689

AN:

151984

Hom.:

13204

Cov.:

AF XY:

0.407

AC XY:

30234

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.379

AC:

15707

AN:

41428

American (AMR)

AF:

0.437

AC:

6678

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1533

AN:

3468

East Asian (EAS)

AF:

0.248

AC:

1281

AN:

5164

South Asian (SAS)

AF:

0.417

AC:

2013

AN:

4822

European-Finnish (FIN)

AF:

0.355

AC:

3754

AN:

10574

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30318

AN:

67938

Other (OTH)

AF:

0.419

AC:

883

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1919

3839

5758

7678

9597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.436

Hom.:

24407

Bravo

AF:

0.417

Asia WGS

AF:

0.319

AC:

1109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.33

(source)

DANN

Benign

0.63

PhyloP100

-2.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over