rs8192335

Positions:

• chr8-22159419-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001385654.1(SFTPC):​c.-434-56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 298,440 control chromosomes in the GnomAD database, including 41 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 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.013 (27 hom.)
• Consequence: SFTPC NM_001385654.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1743/152288) while in subpopulation NFE AF= 0.0187 (1270/68028). AF 95% confidence interval is 0.0178. There are 14 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPC	NM_001385654.1	c.-434-56G>T		intron_variant			NP_001372583.1
SFTPC	NM_001385655.1	c.-434-56G>T		intron_variant			NP_001372584.1
SFTPC	NM_001385656.1	c.-434-56G>T		intron_variant			NP_001372585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPC	ENST00000522880.1	n.764-56G>T		intron_variant, non_coding_transcript_variant		3
SFTPC	ENST00000524318.3	n.359-56G>T		intron_variant, non_coding_transcript_variant		3
SFTPC	ENST00000524350.1	n.214-56G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1744 AN: 152170 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0127 AC: 1850 AN: 146152 Hom.: 27 AF XY: 0.0109 AC XY: 873 AN XY: 80446

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00343

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00330

Gnomad4 FIN exome AF: 0.00461

Gnomad4 NFE exome AF: 0.0178

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0114 AC: 1743 AN: 152288 Hom.: 14 Cov.: 32 AF XY: 0.0111 AC XY: 825 AN XY: 74452

Gnomad4 AFR AF: 0.00322

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0133 Hom.: 4

Bravo AF: 0.0122

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192335; hg19: chr8-22016932;