Genetic Variant SFTPB:c.1002+176A>G (chr2-85663170-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000542.5(SFTPB):c.1002+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,084 control chromosomes in the GnomAD database, including 18,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 18682 hom., cov: 33)

Consequence

SFTPB
NM_000542.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.20

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-85663170-T-C is Benign according to our data. Variant chr2-85663170-T-C is described in ClinVar as [Benign]. Clinvar id is 1272295.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPB	NM_000542.5 link	c.1002+176A>G		intron_variant	Intron 8 of 10	ENST00000519937.7	NP_000533.4	P07988D6W5L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7 link	c.1002+176A>G		intron_variant	Intron 8 of 10	1	NM_000542.5	ENSP00000428719.2		P07988

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69686

AN:

151966

Hom.:

18628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.749

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.459

AC:

69802

AN:

152084

Hom.:

18682

Cov.:

AF XY:

0.453

AC XY:

33665

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.749

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.410

Hom.:

2935

Bravo

AF:

0.481

Asia WGS

AF:

0.382

AC:

1330

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.64

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over