Variant chr2-85661170-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000542.5(SFTPB):c.*19+284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 1166 hom., cov: 0)

Exomes 𝑓: 0.0099 ( 187 hom. )

Consequence

SFTPB
NM_000542.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.377

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 2-85661170-A-G is Benign according to our data. Variant chr2-85661170-A-G is described in ClinVar as [Benign]. Clinvar id is 1244287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPB	NM_000542.5 link	c.*19+284T>C		intron_variant		ENST00000519937.7	NP_000533.4	P07988D6W5L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7 link	c.*19+284T>C		intron_variant		1	NM_000542.5	ENSP00000428719.2		P07988

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

10170

AN:

32392

Hom.:

1165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.0227

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.00794

Gnomad FIN

AF:

0.00171

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.00818

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.00988

AC:

1909

AN:

193208

Hom.:

187

Cov.:

AF XY:

0.00794

AC XY:

818

AN XY:

103062

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.00259

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000759

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000700

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.314

AC:

10185

AN:

32442

Hom.:

1166

Cov.:

AF XY:

0.308

AC XY:

4776

AN XY:

15530

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.0227

Gnomad4 EAS

AF:

0.00180

Gnomad4 SAS

AF:

0.00598

Gnomad4 FIN

AF:

0.00171

Gnomad4 NFE

AF:

0.00818

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.0137

Hom.:

181

Bravo

AF:

0.0812

Asia WGS

AF:

0.0190

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.0

DANN

Benign

0.58

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