rs3024815

Variant names:

• chr2-85661170-A-G
• rs3024815
• NM_000542.5:c.*19+284T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377
• Publications: 1 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*19+284T>C		intron	N/A	NP_000533.4
	SFTPB	NM_198843.3		c.*19+284T>C		intron	N/A	NP_942140.3	P07988
	SFTPB	NM_001367281.1		c.1002+2176T>C		intron	N/A	NP_001354210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.*19+284T>C		intron	N/A	ENSP00000428719.2	P07988
	SFTPB	ENST00000393822.7	TSL:1	c.*19+284T>C		intron	N/A	ENSP00000377409.4	P07988
	SFTPB	ENST00000409383.7	TSL:1	c.*19+284T>C		intron	N/A	ENSP00000386346.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 10170 AN: 32392 Hom.: 1165 Cov.: 0

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.: 0 AF XY: 0.00794 AC XY: 818 AN XY: 103062

African (AFR) AF: 0.249 AC: 1475 AN: 5914

American (AMR) AF: 0.0165 AC: 186 AN: 11274

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 13 AN: 5022

East Asian (EAS) AF: 0.00 AC: 0 AN: 10102

South Asian (SAS) AF: 0.000759 AC: 24 AN: 31624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9664

Middle Eastern (MID) AF: 0.00573 AC: 4 AN: 698

European-Non Finnish (NFE) AF: 0.000700 AC: 76 AN: 108620

Other (OTH) AF: 0.0127 AC: 131 AN: 10290

GnomAD4 genome AF: 0.314 AC: 10185 AN: 32442 Hom.: 1166 Cov.: 0 AF XY: 0.308 AC XY: 4776 AN XY: 15530

African (AFR) AF: 0.502 AC: 9623 AN: 19174

American (AMR) AF: 0.195 AC: 374 AN: 1914

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 11 AN: 484

East Asian (EAS) AF: 0.00180 AC: 1 AN: 556

South Asian (SAS) AF: 0.00598 AC: 3 AN: 502

European-Finnish (FIN) AF: 0.00171 AC: 1 AN: 586

Middle Eastern (MID) AF: 0.143 AC: 6 AN: 42

European-Non Finnish (NFE) AF: 0.00818 AC: 71 AN: 8680

Other (OTH) AF: 0.218 AC: 95 AN: 436

Alfa AF: 0.0215 Hom.: 457

Bravo AF: 0.0812

Asia WGS AF: 0.0190 AC: 66 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3024815; hg19: chr2-85888293;