chr17-1766736-G-T

Variant names:

• chr17-1766736-G-T
• rs79424054
• NM_002615.7:c.-8-167G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002615.7(SERPINF1):​c.-8-167G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 626,622 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (28 hom., cov: 27)
  • Exomes 𝑓: 0.018 (107 hom.)
• Consequence: SERPINF1 NM_002615.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-1766736-G-T is Benign according to our data. Variant chr17-1766736-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1194480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0151 (2248/149164) while in subpopulation NFE AF = 0.022 (1482/67388). AF 95% confidence interval is 0.0211. There are 28 homozygotes in GnomAd4. There are 1131 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 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.-8-167G>T		intron	N/A	NP_002606.3
	SERPINF1	NM_001329903.2		c.-8-167G>T		intron	N/A	NP_001316832.1	A0A140VKF3
	SERPINF1	NM_001329904.2		c.-477-3116G>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.-8-167G>T		intron	N/A	ENSP00000254722.4	P36955
	SERPINF1	ENST00000960888.1		c.-32G>T		5_prime_UTR	Exon 1 of 8	ENSP00000630947.1
	SERPINF1	ENST00000869424.1		c.-8-167G>T		intron	N/A	ENSP00000539483.1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2247 AN: 149074 Hom.: 28 Cov.: 27

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00699

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0137

GnomAD4 exome AF: 0.0180 AC: 8580 AN: 477458 Hom.: 107 Cov.: 5 AF XY: 0.0171 AC XY: 4290 AN XY: 250626

African (AFR) AF: 0.00332 AC: 46 AN: 13858

American (AMR) AF: 0.00825 AC: 202 AN: 24476

Ashkenazi Jewish (ASJ) AF: 0.00286 AC: 42 AN: 14706

East Asian (EAS) AF: 0.0000325 AC: 1 AN: 30782

South Asian (SAS) AF: 0.00770 AC: 371 AN: 48174

European-Finnish (FIN) AF: 0.0420 AC: 1288 AN: 30690

Middle Eastern (MID) AF: 0.00443 AC: 9 AN: 2032

European-Non Finnish (NFE) AF: 0.0215 AC: 6135 AN: 285544

Other (OTH) AF: 0.0179 AC: 486 AN: 27196

GnomAD4 genome AF: 0.0151 AC: 2248 AN: 149164 Hom.: 28 Cov.: 27 AF XY: 0.0156 AC XY: 1131 AN XY: 72608

African (AFR) AF: 0.00339 AC: 137 AN: 40428

American (AMR) AF: 0.00870 AC: 128 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 11 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00700 AC: 33 AN: 4712

European-Finnish (FIN) AF: 0.0405 AC: 412 AN: 10172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0220 AC: 1482 AN: 67388

Other (OTH) AF: 0.0136 AC: 28 AN: 2066

Alfa AF: 0.0167 Hom.: 6

Bravo AF: 0.0129

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		2.2
PromoterAI		0.066	Neutral
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: rs79424054; hg19: chr17-1670030;