dbSNP rs367661082: SFTPB:p.Arg236Arg (chr2-85663812-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BS1BS2

The NM_000542.5(SFTPB):c.708C>T(p.Arg236Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,599,064 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 8 hom. )

Consequence

SFTPB
NM_000542.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.550

Publications

1 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 -17 ACMG points.

BP6

Variant 2-85663812-G-A is Benign according to our data. Variant chr2-85663812-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000499 (76/152332) while in subpopulation SAS AF = 0.011 (53/4834). AF 95% confidence interval is 0.00861. There are 2 homozygotes in GnomAd4. There are 48 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SFTPB	NM_000542.5	MANE Select	c.708C>T	p.Arg236Arg	synonymous	Exon 7 of 11	NP_000533.4
SFTPB	NM_198843.3		c.708C>T	p.Arg236Arg	synonymous	Exon 8 of 12	NP_942140.3	P07988
SFTPB	NM_001367281.1		c.708C>T	p.Arg236Arg	synonymous	Exon 7 of 9	NP_001354210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.708C>T	p.Arg236Arg	synonymous	Exon 7 of 11	ENSP00000428719.2	P07988
SFTPB	ENST00000393822.7	TSL:1	c.708C>T	p.Arg236Arg	synonymous	Exon 8 of 12	ENSP00000377409.4	P07988
SFTPB	ENST00000409383.7	TSL:1	c.708C>T	p.Arg236Arg	synonymous	Exon 8 of 12	ENSP00000386346.2

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00119

AC:

255

AN:

214316

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.0000788

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00195

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000930

GnomAD4 exome

AF:

0.000599

AC:

866

AN:

1446732

Hom.:

Cov.:

AF XY:

0.000829

AC XY:

596

AN XY:

718816

show subpopulations

African (AFR)

AF:

0.0000903

AC:

AN:

33220

American (AMR)

AF:

0.0000232

AC:

AN:

43030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25846

East Asian (EAS)

AF:

0.00338

AC:

132

AN:

39044

South Asian (SAS)

AF:

0.00791

AC:

667

AN:

84290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5344

European-Non Finnish (NFE)

AF:

0.00000813

AC:

AN:

1106700

Other (OTH)

AF:

0.000903

AC:

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000499

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00328

AC:

AN:

5188

South Asian (SAS)

AF:

0.0110

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000299

Hom.:

Bravo

AF:

0.000181

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

-0.48

CADD

Benign

9.1

(source)

DANN

Benign

0.64

PhyloP100

0.55

PromoterAI

0.034

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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