1-16977094-C-T

Position:

• chr1-16977094-C-T

Variant summary

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

The NM_002403.4(MFAP2):​c.127+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,088 control chromosomes in the GnomAD database, including 263,794 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 0.48 (18809 hom., cov: 32)
  • Exomes 𝑓: 0.57 (244985 hom.)
• Consequence: MFAP2 NM_002403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFAP2	NM_002403.4	c.127+15G>A		intron_variant		ENST00000375535.4
LOC105376806	XR_947003.3	n.702+532C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFAP2	ENST00000375535.4	c.127+15G>A		intron_variant		1	NM_002403.4	A1
	ENST00000654887.1	n.261+532C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72256 AN: 151800 Hom.: 18806 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.499

GnomAD3 exomes AF: 0.515 AC: 128742 AN: 249902 Hom.: 34720 AF XY: 0.521 AC XY: 70340 AN XY: 135118

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.493

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.573 AC: 836681 AN: 1461170 Hom.: 244985 Cov.: 46 AF XY: 0.571 AC XY: 414948 AN XY: 726868

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.476 AC: 72265 AN: 151918 Hom.: 18809 Cov.: 32 AF XY: 0.469 AC XY: 34866 AN XY: 74264

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.493

Alfa AF: 0.538 Hom.: 8213

Bravo AF: 0.469

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.71

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: rs2235932; hg19: chr1-17303589; COSMIC: COSV65003666; COSMIC: COSV65003666;