17-1770111-G-T

Variant names:

• chr17-1770111-G-T
• rs12603825
• NM_002615.7:c.283+61G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002615.7(SERPINF1):​c.283+61G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,415,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 29 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.283+61G>T		intron	N/A	NP_002606.3
	SERPINF1	NM_001329903.2		c.283+61G>T		intron	N/A	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.-279+61G>T		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.283+61G>T		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000869424.1		c.283+61G>T		intron	N/A	ENSP00000539483.1
	SERPINF1	ENST00000869426.1		c.283+61G>T		intron	N/A	ENSP00000539485.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1415534 Hom.: 0 AF XY: 0.00000425 AC XY: 3 AN XY: 706126

African (AFR) AF: 0.00 AC: 0 AN: 32292

American (AMR) AF: 0.00 AC: 0 AN: 43676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.00 AC: 0 AN: 84970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1074744

Other (OTH) AF: 0.00 AC: 0 AN: 58862

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 3224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.92
DANN	Benign	0.54
PhyloP100		-0.54

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: rs12603825; hg19: chr17-1673405;