rs11658342

chr17-1769810-G-Achr17-1769810-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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209

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=-0.81).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7	c.85-42G>A		intron_variant		ENST00000254722.9
SERPINF1	NM_001329903.2	c.85-42G>A		intron_variant
SERPINF1	NM_001329904.2	c.-477-42G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9	c.85-42G>A		intron_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43112 AN: 152028 Hom.: 7044 Cov.: 33

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

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.: 28 AF XY: 0.350 AC XY: 253623 AN XY: 723814

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.: 33 AF XY: 0.281 AC XY: 20887 AN XY: 74396

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: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	-0.81
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

Other links and lift over

dbSNP: rs11658342; hg19: chr17-1673104; COSMIC: COSV54616140; COSMIC: COSV54616140;