rs761422

Positions:

• chr1-16975285-A-G
• chr1-16975285-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

MFAP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP2	NM_002403.4	c.432T>C	p.His144His	synonymous_variant	8/9	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4	c.432T>C	p.His144His	synonymous_variant	8/9	1	NM_002403.4	ENSP00000364685.3
MFAP2	ENST00000375534.7	c.429T>C	p.His143His	synonymous_variant	7/8	2		ENSP00000364684.3
MFAP2	ENST00000490075.5	n.1833T>C		non_coding_transcript_exon_variant	5/6	2

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

GnomAD3 exomes AF: 0.446 AC: 111373 AN: 249980 Hom.: 25408 AF XY: 0.445 AC XY: 60178 AN XY: 135098

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 SAS exome AF: 0.446

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

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.456

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

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.458

Alfa AF: 0.473 Hom.: 33202

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.76
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs761422; hg19: chr1-17301780; COSMIC: COSV65003823; COSMIC: COSV65003823;