rs12603825

Positions:

• chr17-1770111-G-A
• chr17-1770111-G-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.283+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,565,842 control chromosomes in the GnomAD database, including 60,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7256 hom., cov: 31)
  • Exomes 𝑓: 0.27 (53329 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.541

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 17-1770111-G-A is Benign according to our data. Variant chr17-1770111-G-A is described in ClinVar as [Benign]. Clinvar id is 1256818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7	c.283+61G>A		intron_variant		ENST00000254722.9
SERPINF1	NM_001329903.2	c.283+61G>A		intron_variant
SERPINF1	NM_001329904.2	c.-279+61G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9	c.283+61G>A		intron_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46114 AN: 151910 Hom.: 7244 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.272 AC: 385184 AN: 1413814 Hom.: 53329 AF XY: 0.271 AC XY: 191214 AN XY: 705316

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.304 AC: 46169 AN: 152028 Hom.: 7256 Cov.: 31 AF XY: 0.302 AC XY: 22407 AN XY: 74304

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.340

Alfa AF: 0.263 Hom.: 2609

Bravo AF: 0.316

Asia WGS AF: 0.262 AC: 914 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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.52

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: rs12603825; hg19: chr17-1673405; COSMIC: COSV54615891; COSMIC: COSV54615891;