1-16980180-C-G

Variant names:

• chr1-16980180-C-G
• rs2284746
• NM_002403.4:c.-42+407G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002403.4(MFAP2):​c.-42+407G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,188 control chromosomes in the GnomAD database, including 14,140 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 0.41 (14140 hom., cov: 28)
• Consequence: MFAP2 NM_002403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 83 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]

ENSG00000226526 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP2	NM_002403.4	c.-42+407G>C		intron_variant	Intron 1 of 8	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4	c.-42+407G>C		intron_variant	Intron 1 of 8	1	NM_002403.4	ENSP00000364685.3
ENSG00000226526	ENST00000446261.1	n.187+1068C>G		intron_variant	Intron 1 of 1	3
MFAP2	ENST00000476788.5	n.46+407G>C		intron_variant	Intron 1 of 5	3
MFAP2	ENST00000490075.5	n.35+407G>C		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61586 AN: 151070 Hom.: 14136 Cov.: 28

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.407 AC: 61586 AN: 151188 Hom.: 14140 Cov.: 28 AF XY: 0.404 AC XY: 29777 AN XY: 73764

African (AFR) AF: 0.197 AC: 8135 AN: 41246

American (AMR) AF: 0.447 AC: 6807 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1610 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1289 AN: 5036

South Asian (SAS) AF: 0.446 AC: 2140 AN: 4794

European-Finnish (FIN) AF: 0.468 AC: 4859 AN: 10380

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35332 AN: 67726

Other (OTH) AF: 0.412 AC: 862 AN: 2094

Alfa AF: 0.462 Hom.: 2173

Bravo AF: 0.395

Asia WGS AF: 0.326 AC: 1131 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		0.075
PromoterAI		0.15	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2284746; hg19: chr1-17306675;