Variant 17-1771833-C-T 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_001329905.2(SERPINF1):c.-161C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,592,992 control chromosomes in the GnomAD database, including 411,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43479 hom., cov: 31)

Exomes 𝑓: 0.71 ( 367667 hom. )

Consequence

SERPINF1
NM_001329905.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.89

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 (BayesDel_noAF=-0.89).

BP6

Variant 17-1771833-C-T is Benign according to our data. Variant chr17-1771833-C-T is described in ClinVar as [Benign]. Clinvar id is 674943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF1	NM_002615.7 link	c.440-39C>T		intron_variant		ENST00000254722.9	NP_002606.3	P36955A0A140VKF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 link	c.440-39C>T		intron_variant		1	NM_002615.7	ENSP00000254722.4		P36955

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114475

AN:

151998

Hom.:

43432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.727

GnomAD3 exomes

AF:

0.726

AC:

174475

AN:

240396

Hom.:

63823

AF XY:

0.717

AC XY:

93591

AN XY:

130552

show subpopulations

Gnomad AFR exome

AF:

0.845

Gnomad AMR exome

AF:

0.788

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.793

Gnomad SAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.706

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.713

AC:

1027090

AN:

1440876

Hom.:

367667

Cov.:

AF XY:

0.709

AC XY:

508871

AN XY:

717548

show subpopulations

Gnomad4 AFR exome

AF:

0.852

Gnomad4 AMR exome

AF:

0.786

Gnomad4 ASJ exome

AF:

0.707

Gnomad4 EAS exome

AF:

0.807

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.745

Gnomad4 NFE exome

AF:

0.708

Gnomad4 OTH exome

AF:

0.710

GnomAD4 genome

AF:

0.753

AC:

114580

AN:

152116

Hom.:

43479

Cov.:

AF XY:

0.752

AC XY:

55959

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.845

Gnomad4 AMR

AF:

0.749

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.635

Gnomad4 FIN

AF:

0.738

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.725

Alfa

AF:

0.714

Hom.:

35208

Bravo

AF:

0.761

Asia WGS

AF:

0.705

AC:

2450

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

Osteogenesis imperfecta type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Medical Molecular Genetics Department, National Research Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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