17-1774962-G-C

Position:

• chr17-1774962-G-C

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.644-96G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,517,950 control chromosomes in the GnomAD database, including 396,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44691 hom., cov: 31)
  • Exomes 𝑓: 0.72 (352294 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.97

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=-0.93).
• BP6: Variant 17-1774962-G-C is Benign according to our data. Variant chr17-1774962-G-C is described in ClinVar as [Benign]. Clinvar id is 674946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.644-96G>C		intron_variant		ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2	c.644-96G>C		intron_variant			NP_001316832.1
SERPINF1	NM_001329904.2	c.83-96G>C		intron_variant			NP_001316833.1
SERPINF1	NM_001329905.2	c.83-96G>C		intron_variant			NP_001316834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.644-96G>C		intron_variant		1	NM_002615.7	ENSP00000254722.4
SERPINF1	ENST00000573763.1	c.43-101G>C		intron_variant		3		ENSP00000461405.1
SERPINF1	ENST00000572048.1	c.83-96G>C		intron_variant		2		ENSP00000458484.1
SERPINF1	ENST00000576406.5	c.83-96G>C		intron_variant		3		ENSP00000461214.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115872 AN: 151918 Hom.: 44638 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.716 AC: 978543 AN: 1365914 Hom.: 352294 AF XY: 0.712 AC XY: 487398 AN XY: 684168

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.792

Gnomad4 ASJ exome AF: 0.706

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.763 AC: 115983 AN: 152036 Hom.: 44691 Cov.: 31 AF XY: 0.762 AC XY: 56602 AN XY: 74288

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.734

Alfa AF: 0.633 Hom.: 1814

Bravo AF: 0.771

Asia WGS AF: 0.704 AC: 2449 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	Jun 19, 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	-0.93
CADD	Benign	0.0060
DANN	Benign	0.41

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: rs2269344; hg19: chr17-1678256; COSMIC: COSV54615635; COSMIC: COSV54615635;