Variant 17-1766736-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002615.7(SERPINF1):c.-8-167G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 626,622 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 28 hom., cov: 27)

Exomes 𝑓: 0.018 ( 107 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-1766736-G-T is Benign according to our data. Variant chr17-1766736-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194480.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0151 (2248/149164) while in subpopulation NFE AF= 0.022 (1482/67388). AF 95% confidence interval is 0.0211. There are 28 homozygotes in gnomad4. There are 1131 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SERPINF1	NM_002615.7 linkuse as main transcript	c.-8-167G>T	intron_variant	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2 linkuse as main transcript	c.-8-167G>T	intron_variant		NP_001316832.1
SERPINF1	NM_001329904.2 linkuse as main transcript	c.-477-3116G>T	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.-8-167G>T		intron_variant		1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2247

AN:

149074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.0188

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00699

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0137

GnomAD4 exome

AF:

0.0180

AC:

8580

AN:

477458

Hom.:

107

Cov.:

AF XY:

0.0171

AC XY:

4290

AN XY:

250626

show subpopulations

Gnomad4 AFR exome

AF:

0.00332

Gnomad4 AMR exome

AF:

0.00825

Gnomad4 ASJ exome

AF:

0.00286

Gnomad4 EAS exome

AF:

0.0000325

Gnomad4 SAS exome

AF:

0.00770

Gnomad4 FIN exome

AF:

0.0420

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0179

GnomAD4 genome

AF:

0.0151

AC:

2248

AN:

149164

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1131

AN XY:

72608

show subpopulations

Gnomad4 AFR

AF:

0.00339

Gnomad4 AMR

AF:

0.00870

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00700

Gnomad4 FIN

AF:

0.0405

Gnomad4 NFE

AF:

0.0220

Gnomad4 OTH

AF:

0.0136

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.2

DANN

Benign

0.68

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