rs2269344

Variant names:

• chr17-1774962-G-C
• rs2269344
• NM_002615.7:c.644-96G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-1774962-G-C
• chr17-1774962-G-A
• chr17-1774962-G-T

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.644-96G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,517,950 control chromosomes in the GnomAD database, including 396,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44691 hom., cov: 31)
  • Exomes 𝑓: 0.72 (352294 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.97
• Publications: 12 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=-0.93).
• BP6: Variant 17-1774962-G-C is Benign according to our data. Variant chr17-1774962-G-C is described in ClinVar as Benign. ClinVar VariationId is 674946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 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.644-96G>C		intron	N/A	NP_002606.3
	SERPINF1	NM_001329903.2		c.644-96G>C		intron	N/A	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.83-96G>C		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.644-96G>C		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000869424.1		c.644-96G>C		intron	N/A	ENSP00000539483.1
	SERPINF1	ENST00000869426.1		c.644-96G>C		intron	N/A	ENSP00000539485.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115872 AN: 151918 Hom.: 44638 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.716 AC: 978543 AN: 1365914 Hom.: 352294 AF XY: 0.712 AC XY: 487398 AN XY: 684168

African (AFR) AF: 0.876 AC: 27468 AN: 31350

American (AMR) AF: 0.792 AC: 35194 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 18002 AN: 25492

East Asian (EAS) AF: 0.799 AC: 31263 AN: 39142

South Asian (SAS) AF: 0.636 AC: 53197 AN: 83602

European-Finnish (FIN) AF: 0.742 AC: 37206 AN: 50176

Middle Eastern (MID) AF: 0.657 AC: 3257 AN: 4958

European-Non Finnish (NFE) AF: 0.711 AC: 732022 AN: 1029538

Other (OTH) AF: 0.716 AC: 40934 AN: 57208

GnomAD4 genome AF: 0.763 AC: 115983 AN: 152036 Hom.: 44691 Cov.: 31 AF XY: 0.762 AC XY: 56602 AN XY: 74288

African (AFR) AF: 0.873 AC: 36232 AN: 41488

American (AMR) AF: 0.757 AC: 11546 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2477 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4064 AN: 5164

South Asian (SAS) AF: 0.641 AC: 3087 AN: 4814

European-Finnish (FIN) AF: 0.738 AC: 7782 AN: 10542

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48357 AN: 67988

Other (OTH) AF: 0.734 AC: 1548 AN: 2108

Alfa AF: 0.633 Hom.: 1814

Bravo AF: 0.771

Asia WGS AF: 0.704 AC: 2449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0060
DANN	Benign	0.41
PhyloP100		-5.0
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: rs2269344; hg19: chr17-1678256; COSMIC: COSV54615635; COSMIC: COSV54615635;