Genetic Variant MFAP5:c.*121T>C (chr12-8647970-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003480.4(MFAP5):c.*121T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 643,990 control chromosomes in the GnomAD database, including 4,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 933 hom., cov: 32)

Exomes 𝑓: 0.11 ( 3737 hom. )

Consequence

MFAP5
NM_003480.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.607

Variant links:

Genes affected

MFAP5 (HGNC:29673): (microfibril associated protein 5) This gene encodes a 25-kD microfibril-associated glycoprotein which is a component of microfibrils of the extracellular matrix. The encoded protein promotes attachment of cells to microfibrils via alpha-V-beta-3 integrin. Deficiency of this gene in mice results in neutropenia. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

MFAP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-8647970-A-G is Benign according to our data. Variant chr12-8647970-A-G is described in ClinVar as [Benign]. Clinvar id is 1271604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP5	NM_003480.4 link	c.*121T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000359478.7	NP_003471.1	Q13361-1B3KW70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFAP5	ENST00000359478 link	c.*121T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_003480.4	ENSP00000352455.2		Q13361-1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15281

AN:

152130

Hom.:

934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0487

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.116

GnomAD4 exome

AF:

0.114

AC:

56109

AN:

491742

Hom.:

3737

Cov.:

AF XY:

0.111

AC XY:

28260

AN XY:

254254

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

Gnomad4 AMR exome

AF:

0.0817

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.000170

Gnomad4 SAS exome

AF:

0.0452

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.100

AC:

15273

AN:

152248

Hom.:

933

Cov.:

AF XY:

0.0983

AC XY:

7314

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0485

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0997

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0466

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.129

Hom.:

2063

Bravo

AF:

0.0985

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.6

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over