dbSNP rs6017667: SPINT4:p.Gly73Ser (chr20-45723981-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_178455.3(SPINT4):c.217G>A(p.Gly73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.396 in 1,609,072 control chromosomes in the GnomAD database, including 134,996 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 18001 hom., cov: 31)

Exomes 𝑓: 0.39 ( 116995 hom. )

Consequence

SPINT4
NM_178455.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.93

Publications

41 publications found

Variant links:

Genes affected

SPINT4 (HGNC:16130): (serine peptidase inhibitor, Kunitz type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPINT4 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=2.9414892E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINT4	NM_178455.3 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 3	ENST00000279058.4	NP_848550.1	Q6UDR6A0A384P5R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINT4	ENST00000279058.4 link	c.217G>A	p.Gly73Ser	missense_variant	Exon 2 of 3	1	NM_178455.3	ENSP00000279058.3		Q6UDR6

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70430

AN:

151820

Hom.:

17980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.472

GnomAD2 exomes

AF:

0.416

AC:

102894

AN:

247122

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.389

AC:

566767

AN:

1457134

Hom.:

116995

Cov.:

AF XY:

0.395

AC XY:

285950

AN XY:

724840

show subpopulations

African (AFR)

AF:

0.686

AC:

22627

AN:

32988

American (AMR)

AF:

0.286

AC:

12485

AN:

43686

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

14234

AN:

26026

East Asian (EAS)

AF:

0.461

AC:

18222

AN:

39548

South Asian (SAS)

AF:

0.547

AC:

46609

AN:

85180

European-Finnish (FIN)

AF:

0.386

AC:

20598

AN:

53344

Middle Eastern (MID)

AF:

0.526

AC:

3022

AN:

5748

European-Non Finnish (NFE)

AF:

0.363

AC:

403073

AN:

1110434

Other (OTH)

AF:

0.430

AC:

25897

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

17652

35305

52957

70610

88262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12986

25972

38958

51944

64930

<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:

0.464

AC:

70489

AN:

151938

Hom.:

18001

Cov.:

AF XY:

0.465

AC XY:

34548

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.673

AC:

27915

AN:

41456

American (AMR)

AF:

0.348

AC:

5304

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1855

AN:

3472

East Asian (EAS)

AF:

0.490

AC:

2534

AN:

5174

South Asian (SAS)

AF:

0.549

AC:

2642

AN:

4812

European-Finnish (FIN)

AF:

0.391

AC:

4119

AN:

10534

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24756

AN:

67920

Other (OTH)

AF:

0.470

AC:

989

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1801

3602

5403

7204

9005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.402

Hom.:

54272

Bravo

AF:

0.468

TwinsUK

AF:

0.374

AC:

1385

ALSPAC

AF:

0.363

AC:

1400

ESP6500AA

AF:

0.641

AC:

2825

ESP6500EA

AF:

0.375

AC:

3223

ExAC

AF:

0.426

AC:

51725

Asia WGS

AF:

0.495

AC:

1723

AN:

3478

EpiCase

AF:

0.383

EpiControl

AF:

0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

MetaRNN

Benign

0.00029

MetaSVM

Benign

-0.88

PhyloP100

3.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.82

MPC

0.87

ClinPred

0.037

GERP RS

4.5

Varity_R

0.89

gMVP

0.95

Mutation Taster

=82/18

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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