rs58697961

Variant names:

• chr17-1762130-G-A
• rs58697961
• NM_002615.7:c.-9+17G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-1762130-G-A
• chr17-1762130-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002615.7(SERPINF1):​c.-9+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,604 control chromosomes in the GnomAD database, including 8,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8694 hom., cov: 33)
  • Exomes 𝑓: 0.41 (34 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.815
• Publications: 8 publications found

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]

SERPINF1 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 6

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-1762130-G-A is Benign according to our data. Variant chr17-1762130-G-A is described in ClinVar as Benign. ClinVar VariationId is 516196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.-9+17G>A		intron_variant	Intron 1 of 7	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329904.2	c.-478+17G>A		intron_variant	Intron 1 of 6		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.-9+17G>A		intron_variant	Intron 1 of 7	1	NM_002615.7	ENSP00000254722.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48455 AN: 152050 Hom.: 8690 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.406 AC: 177 AN: 436 Hom.: 34 Cov.: 0 AF XY: 0.396 AC XY: 126 AN XY: 318

African (AFR) AF: 0.357 AC: 5 AN: 14

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2 AN: 10

East Asian (EAS) AF: 0.643 AC: 9 AN: 14

South Asian (SAS) AF: 0.625 AC: 5 AN: 8

European-Finnish (FIN) AF: 0.533 AC: 16 AN: 30

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.383 AC: 128 AN: 334

Other (OTH) AF: 0.389 AC: 7 AN: 18

GnomAD4 genome AF: 0.319 AC: 48471 AN: 152168 Hom.: 8694 Cov.: 33 AF XY: 0.327 AC XY: 24319 AN XY: 74396

African (AFR) AF: 0.161 AC: 6698 AN: 41538

American (AMR) AF: 0.408 AC: 6240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2483 AN: 5154

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4818

European-Finnish (FIN) AF: 0.464 AC: 4916 AN: 10592

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24020 AN: 67996

Other (OTH) AF: 0.300 AC: 634 AN: 2114

Alfa AF: 0.336 Hom.: 1203

Bravo AF: 0.306

Asia WGS AF: 0.470 AC: 1630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.9
DANN	Benign	0.86
PhyloP100		-0.81
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58697961; hg19: chr17-1665424;