18-63723127-T-C

Position:

• chr18-63723127-T-C

Variant summary

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

The NM_001370475.1(SERPINB11):​c.907T>C​(p.Ser303Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,605,716 control chromosomes in the GnomAD database, including 430,452 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 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 0.73 (40542 hom., cov: 31)
  • Exomes 𝑓: 0.73 (389910 hom.)
• Consequence: SERPINB11 NM_001370475.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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]

SERPINB11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7048577E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.907T>C	p.Ser303Pro	missense_variant	8/8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.907T>C	p.Ser303Pro	missense_variant	9/9		NP_536723.2
SERPINB11	NM_001291278.2	c.646T>C	p.Ser216Pro	missense_variant	6/6		NP_001278207.1
SERPINB11	NM_001291279.2	c.382T>C	p.Ser128Pro	missense_variant	7/7		NP_001278208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.907T>C	p.Ser303Pro	missense_variant	8/8	2	NM_001370475.1	ENSP00000441497.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110792 AN: 151902 Hom.: 40501 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.712

GnomAD3 exomes AF: 0.734 AC: 174322 AN: 237550 Hom.: 64260 AF XY: 0.731 AC XY: 93970 AN XY: 128612

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.751

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.870

Gnomad SAS exome AF: 0.696

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.731 AC: 1063376 AN: 1453696 Hom.: 389910 Cov.: 50 AF XY: 0.730 AC XY: 527368 AN XY: 722506

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.886

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.748

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.729 AC: 110892 AN: 152020 Hom.: 40542 Cov.: 31 AF XY: 0.732 AC XY: 54415 AN XY: 74300

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.715

Alfa AF: 0.722 Hom.: 26570

Bravo AF: 0.729

TwinsUK AF: 0.750 AC: 2780

ALSPAC AF: 0.728 AC: 2807

ESP6500AA AF: 0.728 AC: 2857

ESP6500EA AF: 0.725 AC: 6066

ExAC AF: 0.726 AC: 87619

Asia WGS AF: 0.800 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.036	.;T;T;T
MetaRNN	Benign	0.0000027	T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	.;N;.;.
REVEL	Benign	0.12
Sift4G	Benign	0.14	T;T;T;T
Vest4		0.14
MPC		0.045
ClinPred		0.056	T
GERP RS		2.3
gMVP		0.66

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: rs1395267; hg19: chr18-61390361; COSMIC: COSV66956518; COSMIC: COSV66956518;