17-1762309-G-A

Position:

• chr17-1762309-G-A

Variant summary

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

The NM_002615.7(SERPINF1):​c.-9+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,570 control chromosomes in the GnomAD database, including 23,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (23374 hom., cov: 33)
  • Exomes 𝑓: 0.58 (73 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

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=-0.81).
• BP6: Variant 17-1762309-G-A is Benign according to our data. Variant chr17-1762309-G-A is described in ClinVar as [Benign]. Clinvar id is 1259367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.-9+196G>A		intron_variant		ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329904.2	c.-478+196G>A		intron_variant			NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.-9+196G>A		intron_variant		1	NM_002615.7	ENSP00000254722	P1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81629 AN: 152034 Hom.: 23371 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.581 AC: 243 AN: 418 Hom.: 73 Cov.: 0 AF XY: 0.558 AC XY: 172 AN XY: 308

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.818

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.537 AC: 81649 AN: 152152 Hom.: 23374 Cov.: 33 AF XY: 0.544 AC XY: 40459 AN XY: 74380

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.548

Alfa AF: 0.584 Hom.: 5449

Bravo AF: 0.520

Asia WGS AF: 0.704 AC: 2445 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.77

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: rs66498906; hg19: chr17-1665603;