chr18-63723127-T-C

Variant names:

• chr18-63723127-T-C
• rs1395267
• NM_001370475.1:c.907T>C

Variant summary

Our verdict is Benign. The variant received -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. 13/17 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
• Publications: 25 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=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 rank	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.907T>C	p.Ser303Pro	missense_variant	Exon 8 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.907T>C	p.Ser303Pro	missense_variant	Exon 9 of 9		NP_536723.2
SERPINB11	NM_001291278.2	c.646T>C	p.Ser216Pro	missense_variant	Exon 6 of 6		NP_001278207.1
SERPINB11	NM_001291279.2	c.382T>C	p.Ser128Pro	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.907T>C	p.Ser303Pro	missense_variant	Exon 8 of 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

GnomAD2 exomes AF: 0.734 AC: 174322 AN: 237550 AF XY: 0.731

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 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

African (AFR) AF: 0.709 AC: 23669 AN: 33362

American (AMR) AF: 0.748 AC: 32388 AN: 43316

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18406 AN: 25846

East Asian (EAS) AF: 0.886 AC: 34988 AN: 39476

South Asian (SAS) AF: 0.700 AC: 59711 AN: 85268

European-Finnish (FIN) AF: 0.748 AC: 39679 AN: 53024

Middle Eastern (MID) AF: 0.684 AC: 3936 AN: 5756

European-Non Finnish (NFE) AF: 0.729 AC: 806926 AN: 1107522

Other (OTH) AF: 0.726 AC: 43673 AN: 60126

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

African (AFR) AF: 0.717 AC: 29691 AN: 41438

American (AMR) AF: 0.728 AC: 11118 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2480 AN: 3466

East Asian (EAS) AF: 0.880 AC: 4542 AN: 5164

South Asian (SAS) AF: 0.701 AC: 3371 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7943 AN: 10580

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

European-Non Finnish (NFE) AF: 0.724 AC: 49224 AN: 67978

Other (OTH) AF: 0.715 AC: 1508 AN: 2110

Alfa AF: 0.724 Hom.: 38713

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
PhyloP100		0.43
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
Mutation Taster		=84/16	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: rs1395267; hg19: chr18-61390361; COSMIC: COSV66956518; COSMIC: COSV66956518;