rs2071021

chr17-1776499-A-Gchr17-1776499-A-T

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.787-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,607,822 control chromosomes in the GnomAD database, including 75,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6133 hom., cov: 31)
  • Exomes 𝑓: 0.30 (69458 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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=-0.8).
• BP6: Variant 17-1776499-A-G is Benign according to our data. Variant chr17-1776499-A-G is described in ClinVar as [Benign]. Clinvar id is 674947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7	c.787-33A>G		intron_variant		ENST00000254722.9
SERPINF1	NM_001329903.2	c.787-33A>G		intron_variant
SERPINF1	NM_001329904.2	c.226-33A>G		intron_variant
SERPINF1	NM_001329905.2	c.226-33A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9	c.787-33A>G		intron_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40925 AN: 151840 Hom.: 6128 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.321 AC: 80311 AN: 250164 Hom.: 13892 AF XY: 0.319 AC XY: 43206 AN XY: 135360

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.353

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.303 AC: 441644 AN: 1455868 Hom.: 69458 Cov.: 29 AF XY: 0.304 AC XY: 220638 AN XY: 724700

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.269 AC: 40942 AN: 151954 Hom.: 6133 Cov.: 31 AF XY: 0.276 AC XY: 20463 AN XY: 74266

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.246

Alfa AF: 0.278 Hom.: 1379

Bravo AF: 0.258

Asia WGS AF: 0.378 AC: 1309 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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	-0.80
Cadd	Benign	3.0
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

Other links and lift over

dbSNP: rs2071021; hg19: chr17-1679793; COSMIC: COSV54615267; COSMIC: COSV54615267;