rs3024793

Positions:

chr2-85668136-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000519937.7(SFTPB):c.48G>A(p.Thr16=) 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
ENST00000519937.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.89

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-85668136-C-T is Benign according to our data. Variant chr2-85668136-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPB	NM_000542.5 linkuse as main transcript	c.48G>A	p.Thr16=	synonymous_variant	1/11	ENST00000519937.7	NP_000533.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7 linkuse as main transcript	c.48G>A	p.Thr16=	synonymous_variant	1/11	1	NM_000542.5	ENSP00000428719	P1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3509

AN:

152128

Hom.:

143

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00598

AC:

931

AN:

155618

Hom.:

AF XY:

0.00442

AC XY:

363

AN XY:

82088

show subpopulations

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 SAS exome

AF:

0.000351

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.:

AF XY:

0.00221

AC XY:

1526

AN XY:

690006

show subpopulations

Gnomad4 AFR exome

AF:

0.0828

Gnomad4 AMR exome

AF:

0.00527

Gnomad4 ASJ exome

AF:

0.000874

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000391

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.00664

GnomAD4 genome

AF:

0.0231

AC:

3510

AN:

152246

Hom.:

143

Cov.:

AF XY:

0.0223

AC XY:

1661

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0789

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0206

Hom.:

321

Bravo

AF:

0.0265

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Thr28Thr in exon 2 of SFTPB: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 12.4% (24/194) of Luh ya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (htt p://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs3024793). -

Surfactant metabolism dysfunction, pulmonary, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary pulmonary alveolar proteinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0080

DANN

Benign

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over