rs761423

Positions:

• chr1-16975177-T-C

Variant summary

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

The ENST00000375535.4(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 ENST00000375535.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-0.91).
• 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/exons	MANE	Protein	UniProt
MFAP2	NM_002403.4	c.448+92A>G		intron_variant		ENST00000375535.4	NP_002394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP2	ENST00000375535.4	c.448+92A>G		intron_variant		1	NM_002403.4	ENSP00000364685	A1
MFAP2	ENST00000375534.7	c.445+92A>G		intron_variant		2		ENSP00000364684	P4
MFAP2	ENST00000490075.5	n.1849+92A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.410

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

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.419

Alfa AF: 0.439 Hom.: 19615

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

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: rs761423; hg19: chr1-17301672;