2-85658890-T-C

Variant names:

• chr2-85658890-T-C
• rs7316
• NM_000542.5:c.*812A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000542.5(SFTPB):​c.*812A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,006 control chromosomes in the GnomAD database, including 1,921 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1921 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFTPB NM_000542.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	NM_000542.5	MANE Select	c.*812A>G		3_prime_UTR	Exon 11 of 11	NP_000533.4
	SFTPB	NM_198843.3		c.*20-35A>G		intron	N/A	NP_942140.3
	SFTPB	NM_001367281.1		c.1003-35A>G		intron	N/A	NP_001354210.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.*812A>G		3_prime_UTR	Exon 11 of 11	ENSP00000428719.2
	SFTPB	ENST00000393822.7	TSL:1	c.*812A>G		3_prime_UTR	Exon 12 of 12	ENSP00000377409.4
	SFTPB	ENST00000409383.7	TSL:1	c.*20-35A>G		intron	N/A	ENSP00000386346.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20817 AN: 151888 Hom.: 1906 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.146

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.137 AC: 20886 AN: 152006 Hom.: 1921 Cov.: 32 AF XY: 0.137 AC XY: 10202 AN XY: 74300

African (AFR) AF: 0.244 AC: 10103 AN: 41420

American (AMR) AF: 0.176 AC: 2691 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 248 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1227 AN: 5152

South Asian (SAS) AF: 0.0706 AC: 340 AN: 4814

European-Finnish (FIN) AF: 0.0518 AC: 549 AN: 10590

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0783 AC: 5326 AN: 68002

Other (OTH) AF: 0.150 AC: 315 AN: 2104

Alfa AF: 0.102 Hom.: 3863

Bravo AF: 0.152

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7316; hg19: chr2-85886013;