2-85668581-C-T

Position:

• chr2-85668581-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000393822.7(SFTPB):​c.-69+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 275,172 control chromosomes in the GnomAD database, including 3,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2353 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1170 hom.)
• Consequence: SFTPB ENST00000393822.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.589

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-85668581-C-T is Benign according to our data. Variant chr2-85668581-C-T is described in ClinVar as [Benign]. Clinvar id is 1271864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPB	NM_198843.3	c.-69+93G>A		intron_variant
SFTPB	XM_047445414.1	c.-33+93G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPB	ENST00000393822.7	c.-69+93G>A		intron_variant		1		P1
SFTPB	ENST00000409383.6	c.-69+93G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24857 AN: 152144 Hom.: 2348 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.126 AC: 15501 AN: 122910 Hom.: 1170 AF XY: 0.130 AC XY: 8236 AN XY: 63372

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0606

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0878

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.163 AC: 24890 AN: 152262 Hom.: 2353 Cov.: 33 AF XY: 0.162 AC XY: 12043 AN XY: 74466

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.154

Alfa AF: 0.141 Hom.: 1673

Bravo AF: 0.170

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2019

This variant is associated with the following publications: (PMID: 16500948) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs3024791; hg19: chr2-85895704;