rs2040349

Positions:

• chr2-85662402-A-C
• chr2-85662402-A-G
• chr2-85662402-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000542.5(SFTPB):​c.1003-293T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 803,572 control chromosomes in the GnomAD database, including 62,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (18646 hom., cov: 31)
  • Exomes 𝑓: 0.36 (44160 hom.)
• Consequence: SFTPB NM_000542.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-85662402-A-C is Benign according to our data. Variant chr2-85662402-A-C is described in ClinVar as [Benign]. Clinvar id is 1273105.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/exons	MANE	UniProt
SFTPB	NM_000542.5	c.1003-293T>G		intron_variant		ENST00000519937.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPB	ENST00000519937.7	c.1003-293T>G		intron_variant		1	NM_000542.5	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69621 AN: 151880 Hom.: 18592 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.360 AC: 234662 AN: 651574 Hom.: 44160 AF XY: 0.358 AC XY: 115639 AN XY: 322934

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.459 AC: 69737 AN: 151998 Hom.: 18646 Cov.: 31 AF XY: 0.453 AC XY: 33636 AN XY: 74296

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.438

Alfa AF: 0.353 Hom.: 9805

Bravo AF: 0.481

Asia WGS AF: 0.382 AC: 1332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs2040349; hg19: chr2-85889525;