rs761423

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-16975177-T-A
• chr1-16975177-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002403.4(MFAP2):​c.448+92A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000863 in 1,159,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: MFAP2 NM_002403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	NM_002403.4	MANE Select	c.448+92A>T		intron	N/A	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.448+92A>T		intron	N/A	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.445+92A>T		intron	N/A	NP_001128719.1	P55001-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	ENST00000375535.4	TSL:1 MANE Select	c.448+92A>T		intron	N/A	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.538+92A>T		intron	N/A	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.511+92A>T		intron	N/A	ENSP00000600390.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.63e-7 AC: 1 AN: 1159134 Hom.: 0 Cov.: 15 AF XY: 0.00000172 AC XY: 1 AN XY: 582260

African (AFR) AF: 0.00 AC: 0 AN: 27894

American (AMR) AF: 0.00 AC: 0 AN: 37966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22064

East Asian (EAS) AF: 0.00 AC: 0 AN: 37462

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 853668

Other (OTH) AF: 0.00 AC: 0 AN: 50144

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.62
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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;