2-85663170-T-C

Variant names:

• chr2-85663170-T-C
• rs2118177
• NM_000542.5:c.1002+176A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000542.5(SFTPB):​c.1002+176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,084 control chromosomes in the GnomAD database, including 18,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18682 hom., cov: 33)
• Consequence: SFTPB NM_000542.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.20
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-85663170-T-C is Benign according to our data. Variant chr2-85663170-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPB	NM_000542.5	c.1002+176A>G		intron_variant	Intron 8 of 10	ENST00000519937.7	NP_000533.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7	c.1002+176A>G		intron_variant	Intron 8 of 10	1	NM_000542.5	ENSP00000428719.2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69686 AN: 151966 Hom.: 18628 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.459 AC: 69802 AN: 152084 Hom.: 18682 Cov.: 33 AF XY: 0.453 AC XY: 33665 AN XY: 74348

African (AFR) AF: 0.749 AC: 31100 AN: 41500

American (AMR) AF: 0.413 AC: 6300 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3466

East Asian (EAS) AF: 0.339 AC: 1755 AN: 5172

South Asian (SAS) AF: 0.319 AC: 1538 AN: 4828

European-Finnish (FIN) AF: 0.277 AC: 2931 AN: 10582

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23857 AN: 67948

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.417 Hom.: 3126

Bravo AF: 0.481

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.45
PhyloP100		-2.2
PromoterAI		0.016	Neutral
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

Other links and lift over

dbSNP: rs2118177; hg19: chr2-85890293; COSMIC: COSV60893505; COSMIC: COSV60893505;