rs12603825

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-1770111-G-A
• chr17-1770111-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.283+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,565,842 control chromosomes in the GnomAD database, including 60,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7256 hom., cov: 31)
  • Exomes 𝑓: 0.27 (53329 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-1770111-G-A is Benign according to our data. Variant chr17-1770111-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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.283+61G>A		intron	N/A	NP_002606.3
	SERPINF1	NM_001329903.2		c.283+61G>A		intron	N/A	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.-279+61G>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.283+61G>A		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000869424.1		c.283+61G>A		intron	N/A	ENSP00000539483.1
	SERPINF1	ENST00000869426.1		c.283+61G>A		intron	N/A	ENSP00000539485.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46114 AN: 151910 Hom.: 7244 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.272 AC: 385184 AN: 1413814 Hom.: 53329 AF XY: 0.271 AC XY: 191214 AN XY: 705316

African (AFR) AF: 0.382 AC: 12328 AN: 32262

American (AMR) AF: 0.322 AC: 14045 AN: 43624

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10033 AN: 25770

East Asian (EAS) AF: 0.252 AC: 9847 AN: 39142

South Asian (SAS) AF: 0.239 AC: 20266 AN: 84922

European-Finnish (FIN) AF: 0.236 AC: 11929 AN: 50518

Middle Eastern (MID) AF: 0.331 AC: 1811 AN: 5466

European-Non Finnish (NFE) AF: 0.268 AC: 288044 AN: 1073294

Other (OTH) AF: 0.287 AC: 16881 AN: 58816

GnomAD4 genome AF: 0.304 AC: 46169 AN: 152028 Hom.: 7256 Cov.: 31 AF XY: 0.302 AC XY: 22407 AN XY: 74304

African (AFR) AF: 0.372 AC: 15413 AN: 41440

American (AMR) AF: 0.333 AC: 5090 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5166

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4814

European-Finnish (FIN) AF: 0.241 AC: 2554 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18413 AN: 67980

Other (OTH) AF: 0.340 AC: 714 AN: 2102

Alfa AF: 0.270 Hom.: 3224

Bravo AF: 0.316

Asia WGS AF: 0.262 AC: 914 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	-0.81
CADD	Benign	6.9
DANN	Benign	0.52
PhyloP100		-0.54
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: rs12603825; hg19: chr17-1673405; COSMIC: COSV54615891; COSMIC: COSV54615891;