rs8192306

Variant names:

• chr8-22158340-A-G
• rs8192306
• NM_001385654.1:c.-435+665A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385654.1(SFTPC):​c.-435+665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,068 control chromosomes in the GnomAD database, including 7,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7125 hom., cov: 33)
• Consequence: SFTPC NM_001385654.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 7 publications found

Genes affected

SFTPC (HGNC:10802): (surfactant protein C) This gene encodes the pulmonary-associated surfactant protein C (SPC), an extremely hydrophobic 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. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 2, also called pulmonary alveolar proteinosis due to surfactant protein C deficiency, and are associated with interstitial lung disease in older infants, children, and adults. Alternatively spliced transcript variants encoding different protein isoforms have been identified.[provided by RefSeq, Feb 2010]

SFTPC Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• chronic respiratory distress with surfactant metabolism deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• SFTPC- related interstitial lung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPC	NM_001385654.1	c.-435+665A>G		intron_variant	Intron 1 of 7		NP_001372583.1
SFTPC	NM_001385655.1	c.-435+665A>G		intron_variant	Intron 1 of 7		NP_001372584.1
SFTPC	NM_001385656.1	c.-435+665A>G		intron_variant	Intron 1 of 6		NP_001372585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPC	ENST00000522880.1	n.763+665A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43916 AN: 151950 Hom.: 7100 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.289 AC: 43981 AN: 152068 Hom.: 7125 Cov.: 33 AF XY: 0.284 AC XY: 21149 AN XY: 74362

African (AFR) AF: 0.421 AC: 17439 AN: 41454

American (AMR) AF: 0.200 AC: 3059 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3466

East Asian (EAS) AF: 0.0471 AC: 244 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1397 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2538 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17514 AN: 67956

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.268 Hom.: 5153

Bravo AF: 0.290

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8192306; hg19: chr8-22015853;