rs1395266

Positions:

• chr18-63723098-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370475.1(SERPINB11):​c.878C>T​(p.Thr293Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,599,906 control chromosomes in the GnomAD database, including 423,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (38075 hom., cov: 31)
  • Exomes 𝑓: 0.73 (385153 hom.)
• Consequence: SERPINB11 NM_001370475.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

Genes affected

SERPINB11 (HGNC:14221): (serpin family B member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.1026794E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB11	NM_001370475.1	c.878C>T	p.Thr293Ile	missense_variant	8/8	ENST00000544088.6
SERPINB11	NM_080475.5	c.878C>T	p.Thr293Ile	missense_variant	9/9
SERPINB11	NM_001291278.2	c.617C>T	p.Thr206Ile	missense_variant	6/6
SERPINB11	NM_001291279.2	c.353C>T	p.Thr118Ile	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB11	ENST00000544088.6	c.878C>T	p.Thr293Ile	missense_variant	8/8	2	NM_001370475.1	P1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107239 AN: 151868 Hom.: 38058 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.698

GnomAD3 exomes AF: 0.723 AC: 166453 AN: 230114 Hom.: 60585 AF XY: 0.721 AC XY: 89628 AN XY: 124350

Gnomad AFR exome AF: 0.631

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.842

Gnomad SAS exome AF: 0.678

Gnomad FIN exome AF: 0.752

Gnomad NFE exome AF: 0.717

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.728 AC: 1054568 AN: 1447918 Hom.: 385153 Cov.: 44 AF XY: 0.727 AC XY: 522563 AN XY: 719118

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.853

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.719

GnomAD4 genome AF: 0.706 AC: 107304 AN: 151988 Hom.: 38075 Cov.: 31 AF XY: 0.709 AC XY: 52620 AN XY: 74266

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.694

Alfa AF: 0.722 Hom.: 70191

Bravo AF: 0.702

TwinsUK AF: 0.749 AC: 2776

ALSPAC AF: 0.727 AC: 2803

ESP6500AA AF: 0.652 AC: 2460

ESP6500EA AF: 0.724 AC: 5990

ExAC AF: 0.713 AC: 86034

Asia WGS AF: 0.762 AC: 2651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.64
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
MetaRNN	Benign	9.1e-7	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.013
MPC		0.012
ClinPred		0.021	T
GERP RS		-0.96
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1395266; hg19: chr18-61390332; COSMIC: COSV66957463; COSMIC: COSV66957463;