1-16976782-C-T

Variant names:

• chr1-16976782-C-T
• rs373784175
• NM_002403.4:c.167G>A

Variant summary

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

The NM_002403.4(MFAP2):​c.167G>A​(p.Arg56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,772 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R56P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (1 hom.)
• Consequence: MFAP2 NM_002403.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 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]

ENSG00000286898 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.080313355).

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.167G>A	p.Arg56Gln	missense	Exon 5 of 9	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.167G>A	p.Arg56Gln	missense	Exon 5 of 9	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.164G>A	p.Arg55Gln	missense	Exon 5 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.167G>A	p.Arg56Gln	missense	Exon 5 of 9	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.167G>A	p.Arg56Gln	missense	Exon 5 of 10	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.230G>A	p.Arg77Gln	missense	Exon 5 of 9	ENSP00000600390.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151974 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251262 AF XY: 0.0000663

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461798 Hom.: 1 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 727200

African (AFR) AF: 0.000149 AC: 5 AN: 33476

American (AMR) AF: 0.000335 AC: 15 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111978

Other (OTH) AF: 0.0000828 AC: 5 AN: 60394

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151974 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74230

African (AFR) AF: 0.000169 AC: 7 AN: 41370

American (AMR) AF: 0.0000656 AC: 1 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.043
Sift	Benign	0.056	T
Sift4G	Benign	0.57	T
Polyphen		0.12	B
Vest4		0.22
MVP		0.088
MPC		0.37
ClinPred		0.019	T
GERP RS		2.8
Varity_R		0.037
gMVP		0.25
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs373784175; hg19: chr1-17303277; COSMIC: COSV105926828; COSMIC: COSV105926828;