17-1771135-T-C

Position:

chr17-1771135-T-C

Variant summary

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

The ENST00000254722.9(SERPINF1):c.390T>C(p.Thr130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,536 control chromosomes in the GnomAD database, including 79,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6433 hom., cov: 31)

Exomes 𝑓: 0.31 ( 72859 hom. )

Consequence

SERPINF1
ENST00000254722.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.16

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-1771135-T-C is Benign according to our data. Variant chr17-1771135-T-C is described in ClinVar as [Benign]. Clinvar id is 322003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1771135-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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.390T>C	p.Thr130=	synonymous_variant	4/8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2 linkuse as main transcript	c.390T>C	p.Thr130=	synonymous_variant	4/8		NP_001316832.1
SERPINF1	NM_001329904.2 linkuse as main transcript	c.-172T>C		5_prime_UTR_variant	3/7		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 linkuse as main transcript	c.390T>C	p.Thr130=	synonymous_variant	4/8	1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42087

AN:

151804

Hom.:

6427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.327

AC:

82109

AN:

251308

Hom.:

14338

AF XY:

0.325

AC XY:

44085

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.359

Gnomad SAS exome

AF:

0.347

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.311

AC:

453879

AN:

1461614

Hom.:

72859

Cov.:

AF XY:

0.311

AC XY:

226406

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.412

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.277

AC:

42106

AN:

151922

Hom.:

6433

Cov.:

AF XY:

0.283

AC XY:

21008

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.379

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.294

Hom.:

13193

Bravo

AF:

0.267

Asia WGS

AF:

0.383

AC:

1326

AN:

3478

EpiCase

AF:

0.296

EpiControl

AF:

0.288

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 type 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.095

DANN

Benign

0.27

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