chr8-22161905-G-A

Position:

• chr8-22161905-G-A

Variant summary

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

The NM_001317778.2(SFTPC):​c.42+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,602,206 control chromosomes in the GnomAD database, including 4,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (432 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3667 hom.)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0900

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-22161905-G-A is Benign according to our data. Variant chr8-22161905-G-A is described in ClinVar as [Benign]. Clinvar id is 1268807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2	c.42+35G>A		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1	c.42+35G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8814 AN: 152106 Hom.: 431 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0580 AC: 14347 AN: 247352 Hom.: 701 AF XY: 0.0585 AC XY: 7863 AN XY: 134304

Gnomad AFR exome AF: 0.0277

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.0244

Gnomad EAS exome AF: 0.00267

Gnomad SAS exome AF: 0.0315

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.0670

Gnomad OTH exome AF: 0.0608

GnomAD4 exome AF: 0.0646 AC: 93734 AN: 1449982 Hom.: 3667 Cov.: 28 AF XY: 0.0635 AC XY: 45853 AN XY: 721966

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.0314

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.00280

Gnomad4 SAS exome AF: 0.0315

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.0683

Gnomad4 OTH exome AF: 0.0563

GnomAD4 genome AF: 0.0579 AC: 8817 AN: 152224 Hom.: 432 Cov.: 32 AF XY: 0.0628 AC XY: 4671 AN XY: 74402

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0573 Hom.: 76

Bravo AF: 0.0450

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.48
DANN	Benign	0.41

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: rs8192340; hg19: chr8-22019418;