17-1766736-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002615.7(SERPINF1):c.-8-167G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 626,622 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (28 hom., cov: 27)
  • Exomes 𝑓: 0.018 (107 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21

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=-0.83).
• BP6: Variant 17-1766736-G-T is Benign according to our data. Variant chr17-1766736-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0151 (2248/149164) while in subpopulation NFE AF= 0.022 (1482/67388). AF 95% confidence interval is 0.0211. There are 28 homozygotes in gnomad4. There are 1131 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF1	NM_002615.7	c.-8-167G>T		intron_variant		ENST00000254722.9
SERPINF1	NM_001329903.2	c.-8-167G>T		intron_variant
SERPINF1	NM_001329904.2	c.-477-3116G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF1	ENST00000254722.9	c.-8-167G>T		intron_variant		1	NM_002615.7	P1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2247 AN: 149074 Hom.: 28 Cov.: 27

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00699

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0137

GnomAD4 exome AF: 0.0180 AC: 8580 AN: 477458 Hom.: 107 Cov.: 5 AF XY: 0.0171 AC XY: 4290 AN XY: 250626

Gnomad4 AFR exome AF: 0.00332

Gnomad4 AMR exome AF: 0.00825

Gnomad4 ASJ exome AF: 0.00286

Gnomad4 EAS exome AF: 0.0000325

Gnomad4 SAS exome AF: 0.00770

Gnomad4 FIN exome AF: 0.0420

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.0151 AC: 2248 AN: 149164 Hom.: 28 Cov.: 27 AF XY: 0.0156 AC XY: 1131 AN XY: 72608

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00318

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00700

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0136

Alfa AF: 0.0192 Hom.: 5

Bravo AF: 0.0129

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.2
Dann	Benign	0.68

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: rs79424054; hg19: chr17-1670030;