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: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002615.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF1	NM_002615.7	MANE Select	c.-9+17G>A		intron	N/A	NP_002606.3
	SERPINF1	NM_001329904.2		c.-478+17G>A		intron	N/A	NP_001316833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF1	ENST00000254722.9	TSL:1 MANE Select	c.-9+17G>A		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000869428.1		c.-267G>A		5_prime_UTR	Exon 1 of 8	ENSP00000539487.1
	SERPINF1	ENST00000571149.5	TSL:3	c.-152G>A		5_prime_UTR	Exon 1 of 3	ENSP00000460905.1	I3L425

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;