17-1776499-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002615.7(SERPINF1):c.787-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,607,822 control chromosomes in the GnomAD database, including 75,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6133 hom., cov: 31)

Exomes 𝑓: 0.30 ( 69458 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00400

Publications

16 publications found

Variant links:

Genes affected

SERPINF1 (HGNC:8824): (serpin family F member 1) This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]

SERPINF1 Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 6
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
osteogenesis imperfecta type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta type 4
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SERPINF1 links:

ENSG00000295186 (HGNC:):

ENSG00000295186 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-1776499-A-G is Benign according to our data. Variant chr17-1776499-A-G is described in ClinVar as Benign. ClinVar VariationId is 674947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7 link	c.787-33A>G	intron_variant	Intron 6 of 7	ENST00000254722.9	NP_002606.3	P36955A0A140VKF3
SERPINF1	NM_001329903.2 link	c.787-33A>G	intron_variant	Intron 6 of 7		NP_001316832.1	P36955A0A140VKF3
SERPINF1	NM_001329904.2 link	c.226-33A>G	intron_variant	Intron 5 of 6		NP_001316833.1
SERPINF1	NM_001329905.2 link	c.226-33A>G	intron_variant	Intron 2 of 3		NP_001316834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 link	c.787-33A>G		intron_variant	Intron 6 of 7	1	NM_002615.7	ENSP00000254722.4		P36955

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40925

AN:

151840

Hom.:

6128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.321

AC:

80311

AN:

250164

AF XY:

0.319

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.353

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.303

AC:

441644

AN:

1455868

Hom.:

69458

Cov.:

AF XY:

0.304

AC XY:

220638

AN XY:

724700

show subpopulations

African (AFR)

AF:

0.135

AC:

4493

AN:

33360

American (AMR)

AF:

0.423

AC:

18908

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6055

AN:

26092

East Asian (EAS)

AF:

0.400

AC:

15884

AN:

39666

South Asian (SAS)

AF:

0.345

AC:

29719

AN:

86152

European-Finnish (FIN)

AF:

0.393

AC:

20667

AN:

52522

Middle Eastern (MID)

AF:

0.238

AC:

1357

AN:

5704

European-Non Finnish (NFE)

AF:

0.295

AC:

327212

AN:

1107462

Other (OTH)

AF:

0.288

AC:

17349

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

17199

34398

51598

68797

85996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10862

21724

32586

43448

54310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.269

AC:

40942

AN:

151954

Hom.:

6133

Cov.:

AF XY:

0.276

AC XY:

20463

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.146

AC:

6045

AN:

41476

American (AMR)

AF:

0.337

AC:

5134

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

831

AN:

3468

East Asian (EAS)

AF:

0.373

AC:

1919

AN:

5138

South Asian (SAS)

AF:

0.353

AC:

1695

AN:

4806

European-Finnish (FIN)

AF:

0.407

AC:

4296

AN:

10552

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20228

AN:

67948

Other (OTH)

AF:

0.246

AC:

517

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1477

2955

4432

5910

7387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

1394

Bravo

AF:

0.258

Asia WGS

AF:

0.378

AC:

1309

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 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

(source)

DANN

Benign

0.60

PhyloP100

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over