chr8-22161905-G-A

Variant names:

• chr8-22161905-G-A
• rs8192340
• NM_001317778.2:c.42+35G>A

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SFTPC	NM_001317778.2	c.42+35G>A		intron_variant	Intron 1 of 5	ENST00000679463.1	NP_001304707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPC	ENST00000679463.1	c.42+35G>A		intron_variant	Intron 1 of 5		NM_001317778.2	ENSP00000505152.1

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

GnomAD2 exomes AF: 0.0580 AC: 14347 AN: 247352 AF XY: 0.0585

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 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 AC: 920 AN: 33240

Gnomad4 AMR exome AF: 0.0314 AC: 1405 AN: 44700

Gnomad4 ASJ exome AF: 0.0259 AC: 675 AN: 26056

Gnomad4 EAS exome AF: 0.00280 AC: 111 AN: 39642

Gnomad4 SAS exome AF: 0.0315 AC: 2712 AN: 86068

Gnomad4 FIN exome AF: 0.173 AC: 9114 AN: 52820

Gnomad4 NFE exome AF: 0.0683 AC: 75259 AN: 1101690

Gnomad4 Remaining exome AF: 0.0563 AC: 3380 AN: 60028

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 AC: 0.0285625 AN: 0.0285625

Gnomad4 AMR AF: 0.0369 AC: 0.0368772 AN: 0.0368772

Gnomad4 ASJ AF: 0.0276 AC: 0.0276498 AN: 0.0276498

Gnomad4 EAS AF: 0.00310 AC: 0.00309837 AN: 0.00309837

Gnomad4 SAS AF: 0.0282 AC: 0.0282041 AN: 0.0282041

Gnomad4 FIN AF: 0.193 AC: 0.193302 AN: 0.193302

Gnomad4 NFE AF: 0.0671 AC: 0.0671216 AN: 0.0671216

Gnomad4 OTH AF: 0.0407 AC: 0.0407197 AN: 0.0407197

Alfa AF: 0.0580 Hom.: 495

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.48
DANN	Benign	0.41
Mutation Taster		=100/0	polymorphism (auto)

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;