rs2040349

Variant names:

• chr2-85662402-A-C
• rs2040349
• NM_000542.5:c.1003-293T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SFTPB	NM_000542.5	c.1003-293T>G		intron_variant	Intron 8 of 10	ENST00000519937.7	NP_000533.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7	c.1003-293T>G		intron_variant	Intron 8 of 10	1	NM_000542.5	ENSP00000428719.2

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

African (AFR) AF: 0.767 AC: 11701 AN: 15256

American (AMR) AF: 0.373 AC: 5048 AN: 13532

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 2997 AN: 10332

East Asian (EAS) AF: 0.325 AC: 5579 AN: 17142

South Asian (SAS) AF: 0.312 AC: 13923 AN: 44636

European-Finnish (FIN) AF: 0.263 AC: 3989 AN: 15140

Middle Eastern (MID) AF: 0.367 AC: 695 AN: 1892

European-Non Finnish (NFE) AF: 0.357 AC: 180439 AN: 505804

Other (OTH) AF: 0.370 AC: 10291 AN: 27840

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

African (AFR) AF: 0.749 AC: 31045 AN: 41456

American (AMR) AF: 0.412 AC: 6295 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1753 AN: 5158

South Asian (SAS) AF: 0.319 AC: 1532 AN: 4806

European-Finnish (FIN) AF: 0.277 AC: 2932 AN: 10574

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23859 AN: 67954

Other (OTH) AF: 0.438 AC: 922 AN: 2106

Alfa AF: 0.375 Hom.: 15026

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

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.75
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2040349; hg19: chr2-85889525;