17-1776708-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002615.7(SERPINF1):c.963T>C(p.Tyr321Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,612,732 control chromosomes in the GnomAD database, including 422,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45174 hom., cov: 25)

Exomes 𝑓: 0.72 ( 376985 hom. )

Consequence

SERPINF1
NM_002615.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.70

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-1776708-T-C is Benign according to our data. Variant chr17-1776708-T-C is described in ClinVar as [Benign]. Clinvar id is 322012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1776708-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7 link	c.963T>C	p.Tyr321Tyr	synonymous_variant	Exon 7 of 8	ENST00000254722.9	NP_002606.3	P36955A0A140VKF3
SERPINF1	NM_001329903.2 link	c.963T>C	p.Tyr321Tyr	synonymous_variant	Exon 7 of 8		NP_001316832.1	P36955A0A140VKF3
SERPINF1	NM_001329904.2 link	c.402T>C	p.Tyr134Tyr	synonymous_variant	Exon 6 of 7		NP_001316833.1
SERPINF1	NM_001329905.2 link	c.402T>C	p.Tyr134Tyr	synonymous_variant	Exon 3 of 4		NP_001316834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 link	c.963T>C	p.Tyr321Tyr	synonymous_variant	Exon 7 of 8	1	NM_002615.7	ENSP00000254722.4		P36955

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

115930

AN:

150796

Hom.:

45118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.896

Gnomad AMI

AF:

0.772

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.739

GnomAD3 exomes

AF:

0.732

AC:

184079

AN:

251460

Hom.:

68037

AF XY:

0.722

AC XY:

98169

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.898

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.794

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.736

Gnomad NFE exome

AF:

0.709

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.716

AC:

1047273

AN:

1461818

Hom.:

376985

Cov.:

AF XY:

0.713

AC XY:

518171

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.901

Gnomad4 AMR exome

AF:

0.793

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.802

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.740

Gnomad4 NFE exome

AF:

0.710

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.769

AC:

116045

AN:

150914

Hom.:

45174

Cov.:

AF XY:

0.768

AC XY:

56499

AN XY:

73608

show subpopulations

Gnomad4 AFR

AF:

0.896

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.787

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.737

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.737

Alfa

AF:

0.735

Hom.:

30529

Bravo

AF:

0.779

Asia WGS

AF:

0.706

AC:

2455

AN:

3478

EpiCase

AF:

0.706

EpiControl

AF:

0.701

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis imperfecta type 6

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Medical Molecular Genetics Department, National Research Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jun 09, 2017

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

-0.85

CADD

Benign

0.026

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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