Variant chr17-1762130-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002615.7(SERPINF1):c.-9+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,604 control chromosomes in the GnomAD database, including 8,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8694 hom., cov: 33)

Exomes 𝑓: 0.41 ( 34 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.815

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 17-1762130-G-A is Benign according to our data. Variant chr17-1762130-G-A is described in ClinVar as [Benign]. Clinvar id is 516196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1762130-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF1	NM_002615.7 linkuse as main transcript	c.-9+17G>A		intron_variant		ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329904.2 linkuse as main transcript	c.-478+17G>A		intron_variant			NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 linkuse as main transcript	c.-9+17G>A		intron_variant		1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48455

AN:

152050

Hom.:

8690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.301

GnomAD4 exome

AF:

0.406

AC:

177

AN:

436

Hom.:

Cov.:

AF XY:

0.396

AC XY:

126

AN XY:

318

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.750

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.643

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.319

AC:

48471

AN:

152168

Hom.:

8694

Cov.:

AF XY:

0.327

AC XY:

24319

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.408

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.482

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.341

Hom.:

1184

Bravo

AF:

0.306

Asia WGS

AF:

0.470

AC:

1630

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.9

DANN

Benign

0.86

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