dbSNP rs11658342: SERPINF1:c.85-42G>A (chr17-1769810-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002615.7(SERPINF1):c.85-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,606,138 control chromosomes in the GnomAD database, including 100,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7040 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93593 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.209

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=-0.81).

BP6

Variant 17-1769810-G-A is Benign according to our data. Variant chr17-1769810-G-A is described in ClinVar as [Benign]. Clinvar id is 674942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7 link	c.85-42G>A	intron_variant	Intron 2 of 7	ENST00000254722.9	NP_002606.3	P36955A0A140VKF3
SERPINF1	NM_001329903.2 link	c.85-42G>A	intron_variant	Intron 2 of 7		NP_001316832.1	P36955A0A140VKF3
SERPINF1	NM_001329904.2 link	c.-477-42G>A	intron_variant	Intron 1 of 6		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 link	c.85-42G>A		intron_variant	Intron 2 of 7	1	NM_002615.7	ENSP00000254722.4		P36955

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43112

AN:

152028

Hom.:

7044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.304

AC:

76044

AN:

250022

Hom.:

12710

AF XY:

0.313

AC XY:

42384

AN XY:

135290

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.352

AC:

512221

AN:

1453992

Hom.:

93593

Cov.:

AF XY:

0.350

AC XY:

253623

AN XY:

723814

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.325

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.283

AC:

43110

AN:

152146

Hom.:

7040

Cov.:

AF XY:

0.281

AC XY:

20887

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.351

Hom.:

17885

Bravo

AF:

0.273

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jun 14, 2018

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

-0.81

CADD

Benign

3.3

DANN

Benign

0.60

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