rs2304566

chr2-85663635-T-Cchr2-85663635-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000542.5(SFTPB):c.856+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,601,346 control chromosomes in the GnomAD database, including 53,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3611 hom., cov: 33)
  • Exomes 𝑓: 0.26 (49636 hom.)
• Consequence: SFTPB NM_000542.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-85663635-T-C is Benign according to our data. Variant chr2-85663635-T-C is described in ClinVar as [Benign]. Clinvar id is 1224829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPB	NM_000542.5	c.856+29A>G		intron_variant		ENST00000519937.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPB	ENST00000519937.7	c.856+29A>G		intron_variant		1	NM_000542.5	P1
SFTPB	ENST00000393822.7	c.856+29A>G		intron_variant		1		P1
SFTPB	ENST00000409383.6	c.856+29A>G		intron_variant		1		P1
SFTPB	ENST00000428225.5	c.845+29A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31693 AN: 151850 Hom.: 3605 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0979

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.212 AC: 47449 AN: 223718 Hom.: 5654 AF XY: 0.221 AC XY: 26780 AN XY: 121354

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0894

Gnomad SAS exome AF: 0.239

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.257 AC: 371821 AN: 1449378 Hom.: 49636 Cov.: 35 AF XY: 0.257 AC XY: 184678 AN XY: 719940

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.0815

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.209 AC: 31703 AN: 151968 Hom.: 3611 Cov.: 33 AF XY: 0.207 AC XY: 15377 AN XY: 74244

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0977

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.212

Alfa AF: 0.219 Hom.: 821

Bravo AF: 0.200

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Surfactant metabolism dysfunction, pulmonary, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.64

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: rs2304566; hg19: chr2-85890758; COSMIC: COSV60894519; COSMIC: COSV60894519;