8-22162299-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.43-275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,958 control chromosomes in the GnomAD database, including 10,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10636 hom., cov: 32)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

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=-0.92).
• BP6: Variant 8-22162299-G-A is Benign according to our data. Variant chr8-22162299-G-A is described in ClinVar as [Benign]. Clinvar id is 1282885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2	c.43-275G>A		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1	c.43-275G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54307 AN: 151838 Hom.: 10605 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.358 AC: 54395 AN: 151958 Hom.: 10636 Cov.: 32 AF XY: 0.359 AC XY: 26711 AN XY: 74306

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.329

Alfa AF: 0.323 Hom.: 1900

Bravo AF: 0.362

Asia WGS AF: 0.313 AC: 1085 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.29
Dann	Benign	0.27

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: rs2236739; hg19: chr8-22019812;