ENST00000869424.1:c.-86C>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 ENST00000869424.1(SERPINF1):c.-86C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0647 in 152,520 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 520 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1 hom. )

Consequence

SERPINF1
ENST00000869424.1 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.13

Publications

18 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:

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=-0.53).

BP6

Variant 17-1762036-C-A is Benign according to our data. Variant chr17-1762036-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000869424.1. 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.-86C>A		upstream_gene	N/A	NP_002606.3
	SERPINF1	NM_001329904.2		c.-555C>A		upstream_gene	N/A	NP_001316833.1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
SERPINF1	ENST00000869424.1	c.-86C>A	5_prime_UTR	Exon 1 of 8	ENSP00000539483.1
SERPINF1	ENST00000869426.1	c.-79C>A	5_prime_UTR	Exon 1 of 8	ENSP00000539485.1
SERPINF1	ENST00000869427.1	c.-110C>A	5_prime_UTR	Exon 1 of 9	ENSP00000539486.1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9832

AN:

152160

Hom.:

517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0923

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0636

GnomAD4 exome

AF:

0.0413

AC:

AN:

242

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

AN XY:

146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.154

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0417

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0250

AC:

AN:

160

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0647

AC:

9855

AN:

152278

Hom.:

520

Cov.:

AF XY:

0.0651

AC XY:

4850

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.135

AC:

5622

AN:

41542

American (AMR)

AF:

0.109

AC:

1660

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.0921

AC:

477

AN:

5180

South Asian (SAS)

AF:

0.0159

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0197

AC:

209

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0217

AC:

1476

AN:

68022

Other (OTH)

AF:

0.0643

AC:

136

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

463

926

1390

1853

2316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0433

Hom.:

501

Bravo

AF:

0.0749

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Osteogenesis imperfecta (1)

Osteogenesis Imperfecta, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

4.1

PromoterAI

-0.22

Neutral

(source)

Mutation Taster

=300/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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