chr2-85663648-T-G

Variant names:

Variant summary

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

The NM_000542.5(SFTPB):c.856+16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 1,606,896 control chromosomes in the GnomAD database, including 682,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67510 hom., cov: 32)

Exomes 𝑓: 0.92 ( 615068 hom. )

Consequence

SFTPB
NM_000542.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.80

Publications

9 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 (BayesDel_noAF=-0.9).

BP6

Variant 2-85663648-T-G is Benign according to our data. Variant chr2-85663648-T-G is described in ClinVar as Benign. ClinVar VariationId is 263205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000542.5. 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_000542.5	MANE Select	c.856+16A>C	intron	N/A	NP_000533.4
SFTPB	NM_198843.3		c.856+16A>C	intron	N/A	NP_942140.3	P07988
SFTPB	NM_001367281.1		c.856+16A>C	intron	N/A	NP_001354210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.856+16A>C	intron	N/A	ENSP00000428719.2	P07988
SFTPB	ENST00000393822.7	TSL:1	c.856+16A>C	intron	N/A	ENSP00000377409.4	P07988
SFTPB	ENST00000409383.7	TSL:1	c.856+16A>C	intron	N/A	ENSP00000386346.2

Frequencies

GnomAD3 genomes

AF:

0.941

AC:

143121

AN:

152104

Hom.:

67449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.967

Gnomad ASJ

AF:

0.964

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.955

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.956

GnomAD2 exomes

AF:

0.937

AC:

217733

AN:

232368

AF XY:

0.935

show subpopulations

Gnomad AFR exome

AF:

0.986

Gnomad AMR exome

AF:

0.971

Gnomad ASJ exome

AF:

0.967

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.900

Gnomad NFE exome

AF:

0.908

Gnomad OTH exome

AF:

0.933

GnomAD4 exome

AF:

0.919

AC:

1337150

AN:

1454674

Hom.:

615068

Cov.:

AF XY:

0.920

AC XY:

664921

AN XY:

722966

show subpopulations

African (AFR)

AF:

0.988

AC:

32991

AN:

33382

American (AMR)

AF:

0.970

AC:

42280

AN:

43594

Ashkenazi Jewish (ASJ)

AF:

0.963

AC:

25009

AN:

25958

East Asian (EAS)

AF:

1.00

AC:

39387

AN:

39392

South Asian (SAS)

AF:

0.951

AC:

80937

AN:

85064

European-Finnish (FIN)

AF:

0.897

AC:

47108

AN:

52542

Middle Eastern (MID)

AF:

0.968

AC:

5566

AN:

5752

European-Non Finnish (NFE)

AF:

0.909

AC:

1007742

AN:

1108876

Other (OTH)

AF:

0.934

AC:

56130

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6163

12326

18488

24651

30814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21450

42900

64350

85800

107250

<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:

0.941

AC:

143243

AN:

152222

Hom.:

67510

Cov.:

AF XY:

0.942

AC XY:

70058

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.984

AC:

40906

AN:

41554

American (AMR)

AF:

0.967

AC:

14789

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.964

AC:

3345

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5166

AN:

5168

South Asian (SAS)

AF:

0.955

AC:

4609

AN:

4824

European-Finnish (FIN)

AF:

0.892

AC:

9465

AN:

10608

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61843

AN:

67986

Other (OTH)

AF:

0.957

AC:

2021

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

432

863

1295

1726

2158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.925

Hom.:

7913

Bravo

AF:

0.949

Asia WGS

AF:

0.984

AC:

3421

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hereditary pulmonary alveolar proteinosis (1)

not specified (1)

Surfactant metabolism dysfunction, pulmonary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

(source)

DANN

Benign

0.34

PhyloP100

-1.8

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over