17-1762036-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000571360.5(SERPINF1):c.-86C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0647 in 152,520 control chromosomes in the GnomAD database, including 521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (520 hom., cov: 33)
  • Exomes 𝑓: 0.041 (1 hom.)
• Consequence: SERPINF1 ENST00000571360.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.13

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-1762036-C-A is Benign according to our data. Variant chr17-1762036-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 321997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1762036-C-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7			upstream_gene_variant		ENST00000254722.9
SERPINF1	NM_001329904.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9			upstream_gene_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9832 AN: 152160 Hom.: 517 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0413 AC: 10 AN: 242 Hom.: 1 Cov.: 0 AF XY: 0.0274 AC XY: 4 AN XY: 146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0647 AC: 9855 AN: 152278 Hom.: 520 Cov.: 33 AF XY: 0.0651 AC XY: 4850 AN XY: 74462

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0486 Hom.: 120

Bravo AF: 0.0749

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Osteogenesis imperfecta Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 09, 2021

- -

Osteogenesis Imperfecta, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

This variant is associated with the following publications: (PMID: 16086313) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs9913583; hg19: chr17-1665330;