1-16975285-A-G

Variant names:

• chr1-16975285-A-G
• rs761422
• NM_002403.4:c.432T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002403.4(MFAP2):​c.432T>C​(p.His144His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,612,558 control chromosomes in the GnomAD database, including 181,000 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 0.46 (15982 hom., cov: 31)
  • Exomes 𝑓: 0.47 (165018 hom.)
• Consequence: MFAP2 NM_002403.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 40 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.372 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	NM_002403.4	MANE Select	c.432T>C	p.His144His	synonymous	Exon 8 of 9	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.432T>C	p.His144His	synonymous	Exon 8 of 9	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.429T>C	p.His143His	synonymous	Exon 8 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.432T>C	p.His144His	synonymous	Exon 8 of 9	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.522T>C	p.His174His	synonymous	Exon 9 of 10	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.495T>C	p.His165His	synonymous	Exon 8 of 9	ENSP00000600390.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69182 AN: 151840 Hom.: 15970 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.463

GnomAD2 exomes AF: 0.446 AC: 111373 AN: 249980 AF XY: 0.445

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.257

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.473

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.472 AC: 689661 AN: 1460600 Hom.: 165018 Cov.: 50 AF XY: 0.471 AC XY: 342134 AN XY: 726542

African (AFR) AF: 0.454 AC: 15181 AN: 33452

American (AMR) AF: 0.483 AC: 21539 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12504 AN: 26066

East Asian (EAS) AF: 0.273 AC: 10840 AN: 39692

South Asian (SAS) AF: 0.444 AC: 38245 AN: 86122

European-Finnish (FIN) AF: 0.387 AC: 20656 AN: 53384

Middle Eastern (MID) AF: 0.462 AC: 2655 AN: 5750

European-Non Finnish (NFE) AF: 0.486 AC: 540564 AN: 1111240

Other (OTH) AF: 0.456 AC: 27477 AN: 60320

GnomAD4 genome AF: 0.456 AC: 69217 AN: 151958 Hom.: 15982 Cov.: 31 AF XY: 0.449 AC XY: 33370 AN XY: 74280

African (AFR) AF: 0.455 AC: 18838 AN: 41424

American (AMR) AF: 0.460 AC: 7014 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3468

East Asian (EAS) AF: 0.249 AC: 1285 AN: 5162

South Asian (SAS) AF: 0.435 AC: 2095 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 4001 AN: 10584

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32843 AN: 67930

Other (OTH) AF: 0.458 AC: 963 AN: 2102

Alfa AF: 0.472 Hom.: 46709

Bravo AF: 0.461

Asia WGS AF: 0.330 AC: 1148 AN: 3478

EpiCase AF: 0.479

EpiControl AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.76
DANN	Benign	0.58
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs761422; hg19: chr1-17301780; COSMIC: COSV65003823; COSMIC: COSV65003823;