8-22161907-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001317778.2(SFTPC):c.42+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,600,204 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (46 hom.)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.516

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=-0.82).
• BP6: Variant 8-22161907-G-A is Benign according to our data. Variant chr8-22161907-G-A is described in ClinVar as [Benign]. Clinvar id is 1283058.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00257 (391/152254) while in subpopulation EAS AF= 0.0472 (243/5152). AF 95% confidence interval is 0.0423. There are 8 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2	c.42+37G>A		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1	c.42+37G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 385 AN: 152136 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00487 AC: 1203 AN: 247172 Hom.: 14 AF XY: 0.00464 AC XY: 623 AN XY: 134202

Gnomad AFR exome AF: 0.000518

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.00518

Gnomad EAS exome AF: 0.0506

Gnomad SAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00398

Gnomad NFE exome AF: 0.000483

Gnomad OTH exome AF: 0.00382

GnomAD4 exome AF: 0.00192 AC: 2775 AN: 1447950 Hom.: 46 Cov.: 27 AF XY: 0.00195 AC XY: 1408 AN XY: 721060

Gnomad4 AFR exome AF: 0.000482

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.00438

Gnomad4 EAS exome AF: 0.0417

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.00360

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.00519

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152254 Hom.: 8 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74432

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0472

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00537

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00190 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.0250 AC: 87 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

May 09, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.8
Dann	Benign	0.58

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: rs78177348; hg19: chr8-22019420; COSMIC: COSV59345303; COSMIC: COSV59345303;