rs8192340

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0900

Publications

6 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

SFTPC-related interstitial lung disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
surfactant metabolism dysfunction, pulmonary, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
chronic respiratory distress with surfactant metabolism deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SFTPC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317778.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPC	NM_001317778.2	MANE Select	c.42+35G>A	intron	N/A	NP_001304707.1	P11686-2
SFTPC	NM_001172410.2		c.42+35G>A	intron	N/A	NP_001165881.1	A0A0S2Z4Q0
SFTPC	NM_001385653.1		c.42+35G>A	intron	N/A	NP_001372582.1	P11686-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPC	ENST00000679463.1	MANE Select	c.42+35G>A	intron	N/A	ENSP00000505152.1	P11686-2
SFTPC	ENST00000318561.7	TSL:1	c.42+35G>A	intron	N/A	ENSP00000316152.3	P11686-1
SFTPC	ENST00000521315.5	TSL:1	c.42+35G>A	intron	N/A	ENSP00000430410.1	P11686-2

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8814

AN:

152106

Hom.:

431

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0635

AC XY:

45853

AN XY:

721966

show subpopulations

African (AFR)

AF:

0.0277

AC:

920

AN:

33240

American (AMR)

AF:

0.0314

AC:

1405

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

675

AN:

26056

East Asian (EAS)

AF:

0.00280

AC:

111

AN:

39642

South Asian (SAS)

AF:

0.0315

AC:

2712

AN:

86068

European-Finnish (FIN)

AF:

0.173

AC:

9114

AN:

52820

Middle Eastern (MID)

AF:

0.0275

AC:

158

AN:

5738

European-Non Finnish (NFE)

AF:

0.0683

AC:

75259

AN:

1101690

Other (OTH)

AF:

0.0563

AC:

3380

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

4255

8511

12766

17022

21277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2734

5468

8202

10936

13670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0579

AC:

8817

AN:

152224

Hom.:

432

Cov.:

AF XY:

0.0628

AC XY:

4671

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0286

AC:

1187

AN:

41558

American (AMR)

AF:

0.0369

AC:

564

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

AN:

3472

East Asian (EAS)

AF:

0.00310

AC:

AN:

5164

South Asian (SAS)

AF:

0.0282

AC:

136

AN:

4822

European-Finnish (FIN)

AF:

0.193

AC:

2049

AN:

10600

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0671

AC:

4564

AN:

67996

Other (OTH)

AF:

0.0407

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

430

859

1289

1718

2148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0580

Hom.:

495

Bravo

AF:

0.0450

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.48

(source)

DANN

Benign

0.41

PhyloP100

0.090

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over