rs2304566

Variant names:

• chr2-85663635-T-C
• rs2304566
• NM_000542.5:c.856+29A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-85663635-T-C
• chr2-85663635-T-G

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -1.39
• Publications: 11 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 -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 VariationId 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 rank	MANE	Protein	UniProt
SFTPB	NM_000542.5	c.856+29A>G		intron_variant	Intron 7 of 10	ENST00000519937.7	NP_000533.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7	c.856+29A>G		intron_variant	Intron 7 of 10	1	NM_000542.5	ENSP00000428719.2

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

GnomAD2 exomes AF: 0.212 AC: 47449 AN: 223718 AF XY: 0.221

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 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

African (AFR) AF: 0.127 AC: 4220 AN: 33306

American (AMR) AF: 0.130 AC: 5525 AN: 42506

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5573 AN: 25872

East Asian (EAS) AF: 0.0815 AC: 3196 AN: 39218

South Asian (SAS) AF: 0.239 AC: 20197 AN: 84586

European-Finnish (FIN) AF: 0.206 AC: 10761 AN: 52132

Middle Eastern (MID) AF: 0.235 AC: 1347 AN: 5742

European-Non Finnish (NFE) AF: 0.277 AC: 306389 AN: 1106084

Other (OTH) AF: 0.244 AC: 14613 AN: 59932

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

African (AFR) AF: 0.130 AC: 5388 AN: 41470

American (AMR) AF: 0.181 AC: 2760 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3468

East Asian (EAS) AF: 0.0977 AC: 502 AN: 5136

South Asian (SAS) AF: 0.236 AC: 1131 AN: 4794

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10576

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18103 AN: 67944

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.210 Hom.: 1335

Bravo AF: 0.200

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Surfactant metabolism dysfunction, pulmonary, 1 Benign:1

Jul 15, 2021

Genome-Nilou Lab

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	-0.83
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-1.4
PromoterAI		-0.00030	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: rs2304566; hg19: chr2-85890758; COSMIC: COSV60894519; COSMIC: COSV60894519;