rs34682912

Variant names:

• chr2-85666719-C-T
• rs34682912
• NM_000542.5:c.291G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-85666719-C-T
• chr2-85666719-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000542.5(SFTPB):​c.291G>A​(p.Glu97Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,860 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (33 hom.)
• Consequence: SFTPB NM_000542.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.123
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.033).
• BP6: Variant 2-85666719-C-T is Benign according to our data. Variant chr2-85666719-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.123 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00274 (417/152180) while in subpopulation SAS AF = 0.00622 (30/4824). AF 95% confidence interval is 0.00448. There are 5 homozygotes in GnomAd4. There are 197 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.291G>A	p.Glu97Glu	synonymous	Exon 4 of 11	NP_000533.4
	SFTPB	NM_198843.3		c.291G>A	p.Glu97Glu	synonymous	Exon 5 of 12	NP_942140.3	P07988
	SFTPB	NM_001367281.1		c.291G>A	p.Glu97Glu	synonymous	Exon 4 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.291G>A	p.Glu97Glu	synonymous	Exon 4 of 11	ENSP00000428719.2	P07988
	SFTPB	ENST00000393822.7	TSL:1	c.291G>A	p.Glu97Glu	synonymous	Exon 5 of 12	ENSP00000377409.4	P07988
	SFTPB	ENST00000409383.7	TSL:1	c.291G>A	p.Glu97Glu	synonymous	Exon 5 of 12	ENSP00000386346.2

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152062 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00384 AC: 965 AN: 251296 AF XY: 0.00431

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.0185

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00345

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00297 AC: 4345 AN: 1461680 Hom.: 33 Cov.: 35 AF XY: 0.00322 AC XY: 2344 AN XY: 727170

African (AFR) AF: 0.00134 AC: 45 AN: 33478

American (AMR) AF: 0.00257 AC: 115 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 462 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00777 AC: 670 AN: 86258

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53366

Middle Eastern (MID) AF: 0.0283 AC: 163 AN: 5766

European-Non Finnish (NFE) AF: 0.00231 AC: 2563 AN: 1111902

Other (OTH) AF: 0.00513 AC: 310 AN: 60382

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152180 Hom.: 5 Cov.: 32 AF XY: 0.00265 AC XY: 197 AN XY: 74394

African (AFR) AF: 0.000650 AC: 27 AN: 41518

American (AMR) AF: 0.00248 AC: 38 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00622 AC: 30 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00303 AC: 206 AN: 67976

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00334 Hom.: 2

Bravo AF: 0.00260

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00468

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hereditary pulmonary alveolar proteinosis (1)
-	-	1	Surfactant metabolism dysfunction, pulmonary, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.12
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34682912; hg19: chr2-85893842;