chr17-1766648-AG-A

Variant names:

• chr17-1766648-AG-A
• rs568782425
• NM_002615.7:c.-8-254delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002615.7(SERPINF1):​c.-8-254delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 405,768 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.08
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 17-1766648-AG-A is Benign according to our data. Variant chr17-1766648-AG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1213484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00309 (471/152246) while in subpopulation AFR AF = 0.0109 (455/41560). AF 95% confidence interval is 0.0101. There are 2 homozygotes in GnomAd4. There are 210 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

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.-8-254delG		intron	N/A	NP_002606.3
	SERPINF1	NM_001329903.2		c.-8-254delG		intron	N/A	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.-477-3203delG		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.-8-254delG		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000960886.1		c.-21delG		5_prime_UTR	Exon 2 of 9	ENSP00000630945.1
	SERPINF1	ENST00000577053.1	TSL:5	c.-21delG		5_prime_UTR	Exon 1 of 4	ENSP00000460842.1	I3L3Z3

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152130 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000363 AC: 92 AN: 253522 Hom.: 2 Cov.: 0 AF XY: 0.000283 AC XY: 37 AN XY: 130896

African (AFR) AF: 0.0103 AC: 75 AN: 7270

American (AMR) AF: 0.000236 AC: 2 AN: 8462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9008

East Asian (EAS) AF: 0.00 AC: 0 AN: 20420

South Asian (SAS) AF: 0.00 AC: 0 AN: 11818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1242

European-Non Finnish (NFE) AF: 0.00000628 AC: 1 AN: 159298

Other (OTH) AF: 0.000850 AC: 14 AN: 16462

GnomAD4 genome AF: 0.00309 AC: 471 AN: 152246 Hom.: 2 Cov.: 31 AF XY: 0.00282 AC XY: 210 AN XY: 74432

African (AFR) AF: 0.0109 AC: 455 AN: 41560

American (AMR) AF: 0.000523 AC: 8 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000642 Hom.: 0

Bravo AF: 0.00357

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

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: rs568782425; hg19: chr17-1669942;