Genetic Variant NM_001370475.1:c.907T>C (chr18-63723127-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.427

Publications

25 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.907T>C	p.Ser303Pro	missense_variant	Exon 8 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5 link	c.907T>C	p.Ser303Pro	missense_variant	Exon 9 of 9		NP_536723.2	Q96P15F5GYW9A9UKE9
SERPINB11	NM_001291278.2 link	c.646T>C	p.Ser216Pro	missense_variant	Exon 6 of 6		NP_001278207.1	Q96P15A0A096LPD5A9UKE9
SERPINB11	NM_001291279.2 link	c.382T>C	p.Ser128Pro	missense_variant	Exon 7 of 7		NP_001278208.1	B4DKT7A9UKE9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6 link	c.907T>C	p.Ser303Pro	missense_variant	Exon 8 of 8	2	NM_001370475.1	ENSP00000441497.1		F5GYW9

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110792

AN:

151902

Hom.:

40501

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.730

AC XY:

527368

AN XY:

722506

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

15774

31547

47321

63094

78868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20060

40120

60180

80240

100300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.729

AC:

110892

AN:

152020

Hom.:

40542

Cov.:

AF XY:

0.732

AC XY:

54415

AN XY:

74300

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1550

3100

4650

6200

7750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.036

.;T;T;T

MetaRNN

Benign

0.0000027

T;T;T;T

MetaSVM

Benign

-0.99

PhyloP100

0.43

PrimateAI

Benign

0.32

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

GERP RS

2.3

gMVP

0.66

Mutation Taster

=84/16

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over