rs2077079

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198843.3(SFTPB):c.-32A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,548,004 control chromosomes in the GnomAD database, including 119,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12030 hom., cov: 33)

Exomes 𝑓: 0.39 ( 107368 hom. )

Consequence

SFTPB
NM_198843.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.28

Publications

43 publications found

Variant links:

Genes affected

SFTPB (HGNC:10801): (surfactant protein B) This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, Feb 2010]

SFTPB Gene-Disease associations (from GenCC):

surfactant metabolism dysfunction, pulmonary, 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

SFTPB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3776293E-4).

BP6

Variant 2-85668215-T-G is Benign according to our data. Variant chr2-85668215-T-G is described in ClinVar as Benign. ClinVar VariationId is 165208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198843.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPB	NM_198843.3		c.-32A>C	5_prime_UTR	Exon 2 of 12	NP_942140.3	P07988
SFTPB	NM_000542.5	MANE Select	c.-32A>C	upstream_gene	N/A	NP_000533.4
SFTPB	NM_001367281.1		c.-32A>C	upstream_gene	N/A	NP_001354210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPB	ENST00000393822.7	TSL:1	c.-32A>C	5_prime_UTR	Exon 2 of 12	ENSP00000377409.4	P07988
SFTPB	ENST00000409383.7	TSL:1	c.-32A>C	5_prime_UTR	Exon 2 of 12	ENSP00000386346.2
SFTPB	ENST00000954904.1		c.-32A>C	5_prime_UTR	Exon 1 of 11	ENSP00000624963.1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59945

AN:

151856

Hom.:

12028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.401

GnomAD2 exomes

AF:

0.411

AC:

63998

AN:

155794

AF XY:

0.413

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.390

AC:

544541

AN:

1396030

Hom.:

107368

Cov.:

AF XY:

0.393

AC XY:

270236

AN XY:

688432

show subpopulations

African (AFR)

AF:

0.375

AC:

11823

AN:

31530

American (AMR)

AF:

0.444

AC:

15849

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

12457

AN:

25168

East Asian (EAS)

AF:

0.507

AC:

18095

AN:

35694

South Asian (SAS)

AF:

0.444

AC:

35136

AN:

79132

European-Finnish (FIN)

AF:

0.312

AC:

15364

AN:

49202

Middle Eastern (MID)

AF:

0.435

AC:

2281

AN:

5248

European-Non Finnish (NFE)

AF:

0.381

AC:

410612

AN:

1076550

Other (OTH)

AF:

0.396

AC:

22924

AN:

57824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16455

32911

49366

65822

82277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13170

26340

39510

52680

65850

<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:

0.395

AC:

59972

AN:

151974

Hom.:

12030

Cov.:

AF XY:

0.393

AC XY:

29193

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.385

AC:

15957

AN:

41438

American (AMR)

AF:

0.411

AC:

6281

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1717

AN:

3470

East Asian (EAS)

AF:

0.510

AC:

2620

AN:

5142

South Asian (SAS)

AF:

0.454

AC:

2186

AN:

4810

European-Finnish (FIN)

AF:

0.323

AC:

3416

AN:

10578

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.388

AC:

26371

AN:

67936

Other (OTH)

AF:

0.402

AC:

849

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1940

3880

5821

7761

9701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.401

Hom.:

16176

Bravo

AF:

0.403

TwinsUK

AF:

0.369

AC:

1368

ALSPAC

AF:

0.362

AC:

1396

ESP6500AA

AF:

0.345

AC:

1343

ESP6500EA

AF:

0.354

AC:

2642

ExAC

AF:

0.309

AC:

11819

Asia WGS

AF:

0.457

AC:

1588

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Hereditary pulmonary alveolar proteinosis (1)

Surfactant metabolism dysfunction, pulmonary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.14

MetaRNN

Benign

0.00024

MetaSVM

Benign

-0.92

PhyloP100

1.3

PrimateAI

Benign

0.31

PROVEAN

Benign

0.47

REVEL

Benign

0.030

Sift

Benign

0.66

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.24

ClinPred

0.00099

GERP RS

2.5

PromoterAI

0.032

Neutral

(source)

gMVP

0.51

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over