rs1136287

Positions:

chr17-1769982-C-T

Variant summary

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

The ENST00000254722.9(SERPINF1):c.215C>T(p.Thr72Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,613,816 control chromosomes in the GnomAD database, including 329,446 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36046 hom., cov: 32)

Exomes 𝑓: 0.63 ( 293400 hom. )

Consequence

SERPINF1
ENST00000254722.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.725

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7483504E-6).

BP6

Variant 17-1769982-C-T is Benign according to our data. Variant chr17-1769982-C-T is described in ClinVar as [Benign]. Clinvar id is 322000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1769982-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINF1	NM_002615.7 linkuse as main transcript	c.215C>T	p.Thr72Met	missense_variant	3/8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2 linkuse as main transcript	c.215C>T	p.Thr72Met	missense_variant	3/8		NP_001316832.1
SERPINF1	NM_001329904.2 linkuse as main transcript	c.-347C>T		5_prime_UTR_variant	2/7		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 linkuse as main transcript	c.215C>T	p.Thr72Met	missense_variant	3/8	1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

103173

AN:

151970

Hom.:

35998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.721

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.702

GnomAD3 exomes

AF:

0.609

AC:

153242

AN:

251434

Hom.:

48150

AF XY:

0.606

AC XY:

82331

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.837

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.723

Gnomad EAS exome

AF:

0.543

Gnomad SAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.649

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.630

AC:

920378

AN:

1461726

Hom.:

293400

Cov.:

AF XY:

0.625

AC XY:

454704

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.848

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.725

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.643

Gnomad4 OTH exome

AF:

0.644

GnomAD4 genome

AF:

0.679

AC:

103276

AN:

152090

Hom.:

36046

Cov.:

AF XY:

0.671

AC XY:

49891

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.835

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.721

Gnomad4 EAS

AF:

0.522

Gnomad4 SAS

AF:

0.480

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.643

Gnomad4 OTH

AF:

0.703

Alfa

AF:

0.653

Hom.:

84464

Bravo

AF:

0.694

TwinsUK

AF:

0.645

AC:

2393

ALSPAC

AF:

0.655

AC:

2525

ESP6500AA

AF:

0.829

AC:

3652

ESP6500EA

AF:

0.652

AC:

5606

ExAC

AF:

0.619

AC:

75103

Asia WGS

AF:

0.498

AC:

1737

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.659

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Osteogenesis imperfecta type 6

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Medical Molecular Genetics Department, National Research Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.2

DANN

Benign

0.92

DEOGEN2

Benign

0.14

T;T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.084

T;T;T;T;T

MetaRNN

Benign

0.0000017

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.97

L;.;.;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.50

N;.;.;.;.

REVEL

Benign

0.28

Sift

Benign

0.27

T;.;.;.;.

Sift4G

Benign

0.19

T;T;T;T;T

Polyphen

0.0050

B;.;.;.;.

Vest4

0.080

MPC

0.072

ClinPred

0.029

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.30

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