rs8192327

Positions:

chr8-22162746-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001317778.2(SFTPC):c.201+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,613,860 control chromosomes in the GnomAD database, including 3,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 368 hom., cov: 33)

Exomes 𝑓: 0.060 ( 3274 hom. )

Consequence

SFTPC
NM_001317778.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.918

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-22162746-G-A is Benign according to our data. Variant chr8-22162746-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2 linkuse as main transcript	c.201+14G>A		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1 linkuse as main transcript	c.201+14G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7515

AN:

152196

Hom.:

368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0610

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0534

AC:

13315

AN:

249388

Hom.:

644

AF XY:

0.0540

AC XY:

7304

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.00891

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00100

Gnomad SAS exome

AF:

0.0307

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.0617

Gnomad OTH exome

AF:

0.0553

GnomAD4 exome

AF:

0.0596

AC:

87089

AN:

1461546

Hom.:

3274

Cov.:

AF XY:

0.0587

AC XY:

42655

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00896

Gnomad4 AMR exome

AF:

0.0271

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.0629

Gnomad4 OTH exome

AF:

0.0517

GnomAD4 genome

AF:

0.0493

AC:

7512

AN:

152314

Hom.:

368

Cov.:

AF XY:

0.0548

AC XY:

4085

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.0341

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.0610

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0525

Hom.:

Bravo

AF:

0.0362

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

201+14G>A in intron 2 of SFTPC: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 5.7% (486/8512) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs8192327). -

Interstitial lung disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pulmonary Surfactant Metabolism Dysfunction, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Osteogenesis Imperfecta, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Surfactant metabolism dysfunction, pulmonary, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over