8-22162380-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001317778.2(SFTPC):c.43-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,066 control chromosomes in the GnomAD database, including 5,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5726 hom., cov: 32)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-22162380-G-A is Benign according to our data. Variant chr8-22162380-G-A is described in ClinVar as [Benign]. Clinvar id is 1244660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2	c.43-194G>A		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1	c.43-194G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40742 AN: 151948 Hom.: 5726 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.268 AC: 40755 AN: 152066 Hom.: 5726 Cov.: 32 AF XY: 0.262 AC XY: 19473 AN XY: 74328

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.283

Alfa AF: 0.257 Hom.: 5423

Bravo AF: 0.273

Asia WGS AF: 0.193 AC: 674 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.88
Cadd	Benign	1.1
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8192325; hg19: chr8-22019893;