rs3024793

Variant names:

• chr2-85668136-C-T
• rs3024793
• NM_000542.5:c.48G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000542.5(SFTPB):​c.48G>A​(p.Thr16Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,551,208 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (143 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (121 hom.)
• Consequence: SFTPB NM_000542.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -5.89
• Publications: 5 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.004).
• BP6: Variant 2-85668136-C-T is Benign according to our data. Variant chr2-85668136-C-T is described in ClinVar as Benign. ClinVar VariationId is 165207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	NM_000542.5	MANE Select	c.48G>A	p.Thr16Thr	synonymous	Exon 1 of 11	NP_000533.4
	SFTPB	NM_198843.3		c.48G>A	p.Thr16Thr	synonymous	Exon 2 of 12	NP_942140.3
	SFTPB	NM_001367281.1		c.48G>A	p.Thr16Thr	synonymous	Exon 1 of 9	NP_001354210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.48G>A	p.Thr16Thr	synonymous	Exon 1 of 11	ENSP00000428719.2
	SFTPB	ENST00000393822.7	TSL:1	c.48G>A	p.Thr16Thr	synonymous	Exon 2 of 12	ENSP00000377409.4
	SFTPB	ENST00000409383.7	TSL:1	c.48G>A	p.Thr16Thr	synonymous	Exon 2 of 12	ENSP00000386346.2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3509 AN: 152128 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.00598 AC: 931 AN: 155618 AF XY: 0.00442

Gnomad AFR exome AF: 0.0868

Gnomad AMR exome AF: 0.00505

Gnomad ASJ exome AF: 0.00118

Gnomad EAS exome AF: 0.000177

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000400

Gnomad OTH exome AF: 0.00318

GnomAD4 exome AF: 0.00251 AC: 3518 AN: 1398962 Hom.: 121 Cov.: 32 AF XY: 0.00221 AC XY: 1526 AN XY: 690006

African (AFR) AF: 0.0828 AC: 2616 AN: 31588

American (AMR) AF: 0.00527 AC: 188 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.000874 AC: 22 AN: 25178

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.000391 AC: 31 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49074

Middle Eastern (MID) AF: 0.00742 AC: 42 AN: 5660

European-Non Finnish (NFE) AF: 0.000215 AC: 232 AN: 1078814

Other (OTH) AF: 0.00664 AC: 385 AN: 57994

GnomAD4 genome AF: 0.0231 AC: 3510 AN: 152246 Hom.: 143 Cov.: 33 AF XY: 0.0223 AC XY: 1661 AN XY: 74434

African (AFR) AF: 0.0789 AC: 3275 AN: 41524

American (AMR) AF: 0.0105 AC: 161 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68016

Other (OTH) AF: 0.0213 AC: 45 AN: 2116

Alfa AF: 0.0206 Hom.: 321

Bravo AF: 0.0265

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hereditary pulmonary alveolar proteinosis (1)
-	-	1	not specified (1)
-	-	1	Surfactant metabolism dysfunction, pulmonary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0080
DANN	Benign	0.31
PhyloP100		-5.9
PromoterAI		-0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3024793; hg19: chr2-85895259;