Genetic Variant SERPINF1:c.-9+196G>A (chr17-1762309-G-A) – ACMG Classification: Benign (-20 pts)

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.-9+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,570 control chromosomes in the GnomAD database, including 23,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23374 hom., cov: 33)

Exomes 𝑓: 0.58 ( 73 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

Publications

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

SERPINF1 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=-0.81).

BP6

Variant 17-1762309-G-A is Benign according to our data. Variant chr17-1762309-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002615.7. 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
	SERPINF1	NM_002615.7	MANE Select	c.-9+196G>A		intron	N/A	NP_002606.3
	SERPINF1	NM_001329904.2		c.-478+196G>A		intron	N/A	NP_001316833.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINF1	ENST00000254722.9	TSL:1 MANE Select	c.-9+196G>A	intron	N/A	ENSP00000254722.4	P36955
SERPINF1	ENST00000869428.1		c.-88G>A	5_prime_UTR	Exon 1 of 8	ENSP00000539487.1
SERPINF1	ENST00000869424.1		c.-9+196G>A	intron	N/A	ENSP00000539483.1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81629

AN:

152034

Hom.:

23371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.546

GnomAD4 exome

AF:

0.581

AC:

243

AN:

418

Hom.:

Cov.:

AF XY:

0.558

AC XY:

172

AN XY:

308

show subpopulations

African (AFR)

AF:

0.313

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.818

AC:

AN:

European-Finnish (FIN)

AF:

0.406

AC:

AN:

Middle Eastern (MID)

AF:

0.667

AC:

AN:

European-Non Finnish (NFE)

AF:

0.599

AC:

194

AN:

324

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.537

AC:

81649

AN:

152152

Hom.:

23374

Cov.:

AF XY:

0.544

AC XY:

40459

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.325

AC:

13499

AN:

41522

American (AMR)

AF:

0.608

AC:

9305

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2040

AN:

3472

East Asian (EAS)

AF:

0.630

AC:

3259

AN:

5172

South Asian (SAS)

AF:

0.740

AC:

3570

AN:

4822

European-Finnish (FIN)

AF:

0.671

AC:

7105

AN:

10590

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41127

AN:

67964

Other (OTH)

AF:

0.548

AC:

1158

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1825

3649

5474

7298

9123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.580

Hom.:

13380

Bravo

AF:

0.520

Asia WGS

AF:

0.704

AC:

2445

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

(source)

DANN

Benign

0.77

PhyloP100

-1.5

PromoterAI

0.038

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over