1-16975177-T-C

Variant names:

• chr1-16975177-T-C
• rs761423
• NM_002403.4:c.448+92A>G

Variant summary

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

The NM_002403.4(MFAP2):​c.448+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,307,838 control chromosomes in the GnomAD database, including 119,310 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 (13204 hom., cov: 31)
  • Exomes 𝑓: 0.42 (106106 hom.)
• Consequence: MFAP2 NM_002403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP2	NM_002403.4	c.448+92A>G		intron_variant	Intron 8 of 8	ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4	c.448+92A>G		intron_variant	Intron 8 of 8	1	NM_002403.4	ENSP00000364685.3
MFAP2	ENST00000375534.7	c.445+92A>G		intron_variant	Intron 7 of 7	2		ENSP00000364684.3
MFAP2	ENST00000490075.5	n.1849+92A>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62666 AN: 151866 Hom.: 13195 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.424 AC: 490102 AN: 1155854 Hom.: 106106 Cov.: 15 AF XY: 0.424 AC XY: 246247 AN XY: 580638

African (AFR) AF: 0.366 AC: 10178 AN: 27832

American (AMR) AF: 0.461 AC: 17481 AN: 37882

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 9703 AN: 22038

East Asian (EAS) AF: 0.271 AC: 10151 AN: 37432

South Asian (SAS) AF: 0.416 AC: 30755 AN: 73898

European-Finnish (FIN) AF: 0.361 AC: 18329 AN: 50744

Middle Eastern (MID) AF: 0.431 AC: 2201 AN: 5106

European-Non Finnish (NFE) AF: 0.436 AC: 370773 AN: 850900

Other (OTH) AF: 0.410 AC: 20531 AN: 50022

GnomAD4 genome AF: 0.412 AC: 62689 AN: 151984 Hom.: 13204 Cov.: 31 AF XY: 0.407 AC XY: 30234 AN XY: 74290

African (AFR) AF: 0.379 AC: 15707 AN: 41428

American (AMR) AF: 0.437 AC: 6678 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1281 AN: 5164

South Asian (SAS) AF: 0.417 AC: 2013 AN: 4822

European-Finnish (FIN) AF: 0.355 AC: 3754 AN: 10574

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30318 AN: 67938

Other (OTH) AF: 0.419 AC: 883 AN: 2108

Alfa AF: 0.436 Hom.: 24407

Bravo AF: 0.417

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.63
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs761423; hg19: chr1-17301672;