1-16974951-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002403.4(MFAP2):c.521C>G(p.Ala174Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 17)
  • Exomes 𝑓: 0.0053 (12 hom.)
• Consequence: MFAP2 NM_002403.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025643706).
• BP6: Variant 1-16974951-G-C is Benign according to our data. Variant chr1-16974951-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638387.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-16974951-G-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFAP2	NM_002403.4	c.521C>G	p.Ala174Gly	missense_variant	9/9	ENST00000375535.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFAP2	ENST00000375535.4	c.521C>G	p.Ala174Gly	missense_variant	9/9	1	NM_002403.4	A1
MFAP2	ENST00000375534.7	c.518C>G	p.Ala173Gly	missense_variant	8/8	2		P4
MFAP2	ENST00000490075.5	n.1922C>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 584 AN: 143204 Hom.: 2 Cov.: 17

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00397

Gnomad ASJ AF: 0.000886

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00142

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.00420

GnomAD3 exomes AF: 0.00362 AC: 509 AN: 140732 Hom.: 1 AF XY: 0.00375 AC XY: 281 AN XY: 74920

Gnomad AFR exome AF: 0.000697

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00105

Gnomad EAS exome AF: 0.0000892

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00118

Gnomad NFE exome AF: 0.00692

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00534 AC: 4467 AN: 835936 Hom.: 12 Cov.: 11 AF XY: 0.00532 AC XY: 2284 AN XY: 429274

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00239

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00693

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.00407 AC: 584 AN: 143314 Hom.: 2 Cov.: 17 AF XY: 0.00408 AC XY: 283 AN XY: 69344

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00397

Gnomad4 ASJ AF: 0.000886

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00142

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.00688

Gnomad4 OTH AF: 0.00416

Alfa AF: 0.00248 Hom.: 1

ExAC AF: 0.00105 AC: 82

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MFAP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.68	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.041
Sift	Benign	0.065	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0030	.;B
Vest4		0.13
MVP		0.10
MPC		0.49
ClinPred		0.0086	T
GERP RS		3.0
Varity_R		0.070
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs201874534; hg19: chr1-17301446;