rs1395266

Variant names:

• chr18-63723098-C-T
• rs1395266
• NM_001370475.1:c.878C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/18 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.878C>T	p.Thr293Ile	missense_variant	Exon 8 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.878C>T	p.Thr293Ile	missense_variant	Exon 9 of 9		NP_536723.2
SERPINB11	NM_001291278.2	c.617C>T	p.Thr206Ile	missense_variant	Exon 6 of 6		NP_001278207.1
SERPINB11	NM_001291279.2	c.353C>T	p.Thr118Ile	missense_variant	Exon 7 of 7		NP_001278208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.878C>T	p.Thr293Ile	missense_variant	Exon 8 of 8	2	NM_001370475.1	ENSP00000441497.1

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

GnomAD2 exomes AF: 0.723 AC: 166453 AN: 230114 AF XY: 0.721

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 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

African (AFR) AF: 0.633 AC: 21049 AN: 33232

American (AMR) AF: 0.743 AC: 31520 AN: 42438

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 18281 AN: 25638

East Asian (EAS) AF: 0.853 AC: 33613 AN: 39414

South Asian (SAS) AF: 0.684 AC: 57621 AN: 84236

European-Finnish (FIN) AF: 0.751 AC: 39632 AN: 52752

Middle Eastern (MID) AF: 0.682 AC: 3913 AN: 5740

European-Non Finnish (NFE) AF: 0.730 AC: 805861 AN: 1104574

Other (OTH) AF: 0.719 AC: 43078 AN: 59894

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

African (AFR) AF: 0.638 AC: 26430 AN: 41436

American (AMR) AF: 0.721 AC: 11004 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4351 AN: 5156

South Asian (SAS) AF: 0.683 AC: 3290 AN: 4820

European-Finnish (FIN) AF: 0.754 AC: 7961 AN: 10556

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49305 AN: 67960

Other (OTH) AF: 0.694 AC: 1466 AN: 2112

Alfa AF: 0.718 Hom.: 85667

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
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.64
DEOGEN2	Benign	0.0	.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.0	.;T;T;T
MetaRNN	Benign	9.1e-7	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;.;.;.
PhyloP100		2.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.0	.;N;.;.
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;.;.;.
Sift4G	Benign	0.22	T;T;T;T
Vest4		0.013
ClinPred		0.021	T
GERP RS		-0.96
gMVP		0.28
Mutation Taster		=99/1	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: rs1395266; hg19: chr18-61390332; COSMIC: COSV66957463; COSMIC: COSV66957463;