rs201874534

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-16974951-G-C
• chr1-16974951-G-A

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• 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: Benign. The variant received -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 VariationId is 2638387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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>G	p.Ala174Gly	missense	Exon 9 of 9	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.521C>G	p.Ala174Gly	missense	Exon 9 of 9	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.518C>G	p.Ala173Gly	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>G	p.Ala174Gly	missense	Exon 9 of 9	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.611C>G	p.Ala204Gly	missense	Exon 10 of 10	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.584C>G	p.Ala195Gly	missense	Exon 9 of 9	ENSP00000600390.1

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

GnomAD2 exomes AF: 0.00362 AC: 509 AN: 140732 AF XY: 0.00375

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 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

African (AFR) AF: 0.00119 AC: 25 AN: 21020

American (AMR) AF: 0.00239 AC: 82 AN: 34286

Ashkenazi Jewish (ASJ) AF: 0.00106 AC: 22 AN: 20852

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

South Asian (SAS) AF: 0.00202 AC: 135 AN: 66670

European-Finnish (FIN) AF: 0.00131 AC: 58 AN: 44248

Middle Eastern (MID) AF: 0.00388 AC: 13 AN: 3348

European-Non Finnish (NFE) AF: 0.00693 AC: 3977 AN: 573476

Other (OTH) AF: 0.00395 AC: 155 AN: 39244

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

African (AFR) AF: 0.00123 AC: 47 AN: 38232

American (AMR) AF: 0.00397 AC: 56 AN: 14118

Ashkenazi Jewish (ASJ) AF: 0.000886 AC: 3 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4668

South Asian (SAS) AF: 0.00142 AC: 6 AN: 4232

European-Finnish (FIN) AF: 0.00103 AC: 10 AN: 9752

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00688 AC: 453 AN: 65822

Other (OTH) AF: 0.00416 AC: 8 AN: 1924

Alfa AF: 0.00248 Hom.: 1

ExAC AF: 0.00105 AC: 82

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.041
Sift	Benign	0.065	T
Sift4G	Benign	0.30	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
Mutation Taster		=99/1	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;