2-85668215-T-G

Position:

chr2-85668215-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000393822.7(SFTPB):c.-32A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,548,004 control chromosomes in the GnomAD database, including 119,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12030 hom., cov: 33)

Exomes 𝑓: 0.39 ( 107368 hom. )

Consequence

SFTPB
ENST00000393822.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.28

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3776293E-4).

BP6

Variant 2-85668215-T-G is Benign according to our data. Variant chr2-85668215-T-G is described in ClinVar as [Benign]. Clinvar id is 165208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85668215-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPB	NM_000542.5 linkuse as main transcript			upstream_gene_variant		ENST00000519937.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPB	ENST00000519937.7 linkuse as main transcript			upstream_gene_variant		1	NM_000542.5	P1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59945

AN:

151856

Hom.:

12028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.401

GnomAD3 exomes

AF:

0.411

AC:

63998

AN:

155794

Hom.:

13387

AF XY:

0.413

AC XY:

33868

AN XY:

82088

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.503

Gnomad SAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.390

AC:

544541

AN:

1396030

Hom.:

107368

Cov.:

AF XY:

0.393

AC XY:

270236

AN XY:

688432

show subpopulations

Gnomad4 AFR exome

AF:

0.375

Gnomad4 AMR exome

AF:

0.444

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.395

AC:

59972

AN:

151974

Hom.:

12030

Cov.:

AF XY:

0.393

AC XY:

29193

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.385

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.403

Hom.:

10292

Bravo

AF:

0.403

TwinsUK

AF:

0.369

AC:

1368

ALSPAC

AF:

0.362

AC:

1396

ESP6500AA

AF:

0.345

AC:

1343

ESP6500EA

AF:

0.354

AC:

2642

ExAC

AF:

0.309

AC:

11819

Asia WGS

AF:

0.457

AC:

1588

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 13, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 26202972, 17071721) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hereditary pulmonary alveolar proteinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2015

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. -

Surfactant metabolism dysfunction, pulmonary, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.14

MetaRNN

Benign

0.00024

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.47

REVEL

Benign

0.030

Sift

Benign

0.66

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.24

ClinPred

0.00099

GERP RS

2.5

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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