rs7592

Positions:

chr8-22164370-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001317778.2(SFTPC):c.*123G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,535,018 control chromosomes in the GnomAD database, including 84,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9680 hom., cov: 35)

Exomes 𝑓: 0.33 ( 75097 hom. )

Consequence

SFTPC
NM_001317778.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.108

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-22164370-G-A is Benign according to our data. Variant chr8-22164370-G-A is described in ClinVar as [Benign]. Clinvar id is 362568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-22164370-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPC	NM_001317778.2 linkuse as main transcript	c.*123G>A		3_prime_UTR_variant	6/6	ENST00000679463.1	NP_001304707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPC	ENST00000679463.1 linkuse as main transcript	c.*123G>A		3_prime_UTR_variant	6/6		NM_001317778.2	ENSP00000505152	A1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53794

AN:

152090

Hom.:

9668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.317

AC:

43123

AN:

136128

Hom.:

7006

AF XY:

0.313

AC XY:

23153

AN XY:

73952

show subpopulations

Gnomad AFR exome

AF:

0.439

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.328

AC:

453522

AN:

1382810

Hom.:

75097

Cov.:

AF XY:

0.327

AC XY:

222990

AN XY:

682330

show subpopulations

Gnomad4 AFR exome

AF:

0.433

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.354

AC:

53839

AN:

152208

Hom.:

9680

Cov.:

AF XY:

0.352

AC XY:

26178

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.340

Hom.:

9258

Bravo

AF:

0.360

Asia WGS

AF:

0.306

AC:

1065

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Surfactant metabolism dysfunction, pulmonary, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.78

CADD

Benign

7.1

DANN

Benign

0.72

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

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