8-22161558-G-A

Position:

• chr8-22161558-G-A

Variant summary

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

The NM_001385654.1(SFTPC):​c.-53-218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 876,452 control chromosomes in the GnomAD database, including 2,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (405 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1672 hom.)
• Consequence: SFTPC NM_001385654.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.254

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 8-22161558-G-A is Benign according to our data. Variant chr8-22161558-G-A is described in ClinVar as [Benign]. Clinvar id is 1221063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPC	NM_001385654.1	c.-53-218G>A		intron_variant			NP_001372583.1
SFTPC	NM_001385655.1	c.-53-218G>A		intron_variant			NP_001372584.1
SFTPC	NM_001385656.1	c.-53-218G>A		intron_variant			NP_001372585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPC	ENST00000524318.3	n.740-218G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7995 AN: 152166 Hom.: 405 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.0609 AC: 44110 AN: 724168 Hom.: 1672 AF XY: 0.0595 AC XY: 21764 AN XY: 366050

Gnomad4 AFR exome AF: 0.00889

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.00288

Gnomad4 SAS exome AF: 0.0311

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.0666

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.0525 AC: 7989 AN: 152284 Hom.: 405 Cov.: 32 AF XY: 0.0576 AC XY: 4289 AN XY: 74454

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0275

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0620 Hom.: 99

Bravo AF: 0.0390

Asia WGS AF: 0.0180 AC: 61 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	-0.64
CADD	Benign	14
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192339; hg19: chr8-22019071;