rs1136287

Variant names:

• chr17-1769982-C-G
• NM_002615.7:c.215C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-1769982-C-G
• chr17-1769982-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002615.7(SERPINF1):​c.215C>G​(p.Thr72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T72M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SERPINF1 NM_002615.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06283358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF1	NM_002615.7	c.215C>G	p.Thr72Arg	missense_variant	Exon 3 of 8	ENST00000254722.9	NP_002606.3
SERPINF1	NM_001329903.2	c.215C>G	p.Thr72Arg	missense_variant	Exon 3 of 8		NP_001316832.1
SERPINF1	NM_001329904.2	c.-347C>G		5_prime_UTR_variant	Exon 2 of 7		NP_001316833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF1	ENST00000254722.9	c.215C>G	p.Thr72Arg	missense_variant	Exon 3 of 8	1	NM_002615.7	ENSP00000254722.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461604 Hom.: 0 Cov.: 74 AF XY: 0.00000963 AC XY: 7 AN XY: 727126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.0070
DANN	Benign	0.67
DEOGEN2	Benign	0.084	T;T;T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.090	T;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.063	T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.47	N;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.1	N;.;.;.;.
REVEL	Benign	0.27
Sift	Benign	0.74	T;.;.;.;.
Sift4G	Benign	0.77	T;T;T;T;T
Polyphen		0.0	B;.;.;.;.
Vest4		0.093
MutPred		0.28		Gain of MoRF binding (P = 0.0665);.;Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);
MVP		0.42
MPC		0.075
ClinPred		0.041	T
GERP RS		-11
Varity_R		0.040
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1673276;