dbSNP rs12603825: SERPINF1:c.283+61G>A (chr17-1770111-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.283+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,565,842 control chromosomes in the GnomAD database, including 60,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7256 hom., cov: 31)

Exomes 𝑓: 0.27 ( 53329 hom. )

Consequence

SERPINF1
NM_002615.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.541

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 17-1770111-G-A is Benign according to our data. Variant chr17-1770111-G-A is described in ClinVar as [Benign]. Clinvar id is 1256818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7 link	c.283+61G>A	intron_variant	Intron 3 of 7	ENST00000254722.9	NP_002606.3	P36955A0A140VKF3
SERPINF1	NM_001329903.2 link	c.283+61G>A	intron_variant	Intron 3 of 7		NP_001316832.1	P36955A0A140VKF3
SERPINF1	NM_001329904.2 link	c.-279+61G>A	intron_variant	Intron 2 of 6		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9 link	c.283+61G>A		intron_variant	Intron 3 of 7	1	NM_002615.7	ENSP00000254722.4		P36955

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46114

AN:

151910

Hom.:

7244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.272

AC:

385184

AN:

1413814

Hom.:

53329

AF XY:

0.271

AC XY:

191214

AN XY:

705316

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.389

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.304

AC:

46169

AN:

152028

Hom.:

7256

Cov.:

AF XY:

0.302

AC XY:

22407

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.372

Gnomad4 AMR

AF:

0.333

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.241

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.263

Hom.:

2609

Bravo

AF:

0.316

Asia WGS

AF:

0.262

AC:

914

AN:

3478

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 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.9

DANN

Benign

0.52

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