1-16974951-G-A

Variant names:

• chr1-16974951-G-A
• rs201874534
• NM_002403.4:c.521C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002403.4(MFAP2):​c.521C>T​(p.Ala174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A174G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFAP2 NM_002403.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10219082).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	NM_002403.4	MANE Select	c.521C>T	p.Ala174Val	missense	Exon 9 of 9	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.521C>T	p.Ala174Val	missense	Exon 9 of 9	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.518C>T	p.Ala173Val	missense	Exon 9 of 9	NP_001128719.1	P55001-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	ENST00000375535.4	TSL:1 MANE Select	c.521C>T	p.Ala174Val	missense	Exon 9 of 9	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.611C>T	p.Ala204Val	missense	Exon 10 of 10	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.584C>T	p.Ala195Val	missense	Exon 9 of 9	ENSP00000600390.1

Frequencies

GnomAD3 genomes AF: 0.00000698 AC: 1 AN: 143210 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 836010 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 429320

African (AFR) AF: 0.00 AC: 0 AN: 21020

American (AMR) AF: 0.00 AC: 0 AN: 34290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20852

East Asian (EAS) AF: 0.00 AC: 0 AN: 32792

South Asian (SAS) AF: 0.00 AC: 0 AN: 66672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3348

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 573538

Other (OTH) AF: 0.00 AC: 0 AN: 39250

GnomAD4 genome AF: 0.00000698 AC: 1 AN: 143210 Hom.: 0 Cov.: 17 AF XY: 0.0000144 AC XY: 1 AN XY: 69226

African (AFR) AF: 0.00 AC: 0 AN: 38118

American (AMR) AF: 0.00 AC: 0 AN: 14098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4678

South Asian (SAS) AF: 0.00 AC: 0 AN: 4238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65836

Other (OTH) AF: 0.00 AC: 0 AN: 1904

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.044	D
Polyphen		0.30	B
Vest4		0.17
MutPred		0.51		Gain of relative solvent accessibility (P = 0.09)
MVP		0.13
MPC		0.31
ClinPred		0.58	D
GERP RS		3.0
Varity_R		0.083
gMVP		0.38
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs201874534; hg19: chr1-17301446;