rs1051225

Positions:

• chr1-16974730-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002403.4(MFAP2):​c.*190A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.36 (636 hom., cov: 3)
  • Exomes 𝑓: 0.46 (24539 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFAP2 NM_002403.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP2	NM_002403.4	c.*190A>G		3_prime_UTR_variant	9/9	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4	c.*190A>G		3_prime_UTR_variant	9/9	1	NM_002403.4	ENSP00000364685	A1
MFAP2	ENST00000375534.7	c.*190A>G		3_prime_UTR_variant	8/8	2		ENSP00000364684	P4
MFAP2	ENST00000490075.5	n.2143A>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 2797 AN: 7766 Hom.: 635 Cov.: 3

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.438

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.460 AC: 101741 AN: 221306 Hom.: 24539 Cov.: 0 AF XY: 0.460 AC XY: 52598 AN XY: 114460

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.360 AC: 2790 AN: 7746 Hom.: 636 Cov.: 3 AF XY: 0.358 AC XY: 1286 AN XY: 3590

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.425

Alfa AF: 0.474 Hom.: 1756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.37

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: rs1051225; hg19: chr1-17301225;