rs58697961

chr17-1762130-G-Achr17-1762130-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002615.7(SERPINF1):c.-9+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,604 control chromosomes in the GnomAD database, including 8,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8694 hom., cov: 33)
  • Exomes 𝑓: 0.41 (34 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.815

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-1762130-G-A is Benign according to our data. Variant chr17-1762130-G-A is described in ClinVar as [Benign]. Clinvar id is 516196.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1762130-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7	c.-9+17G>A		intron_variant		ENST00000254722.9
SERPINF1	NM_001329904.2	c.-478+17G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9	c.-9+17G>A		intron_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48455 AN: 152050 Hom.: 8690 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.406 AC: 177 AN: 436 Hom.: 34 Cov.: 0 AF XY: 0.396 AC XY: 126 AN XY: 318

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.319 AC: 48471 AN: 152168 Hom.: 8694 Cov.: 33 AF XY: 0.327 AC XY: 24319 AN XY: 74396

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.300

Alfa AF: 0.341 Hom.: 1184

Bravo AF: 0.306

Asia WGS AF: 0.470 AC: 1630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2017

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	-0.65
Cadd	Benign	4.9
Dann	Benign	0.86

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: rs58697961; hg19: chr17-1665424;