Variant chr8-22162553-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001317778.2(SFTPC):c.43-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,611,794 control chromosomes in the GnomAD database, including 169,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20258 hom., cov: 32)

Exomes 𝑓: 0.45 ( 148919 hom. )

Consequence

SFTPC
NM_001317778.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.05

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=-0.89).

BP6

Variant 8-22162553-T-C is Benign according to our data. Variant chr8-22162553-T-C is described in ClinVar as [Benign]. Clinvar id is 1272642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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.43-21T>C		intron_variant		ENST00000679463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPC	ENST00000679463.1 linkuse as main transcript	c.43-21T>C		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76426

AN:

151966

Hom.:

20223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.494

AC:

122960

AN:

248714

Hom.:

32051

AF XY:

0.488

AC XY:

65930

AN XY:

134996

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.795

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.446

AC:

650445

AN:

1459706

Hom.:

148919

Cov.:

AF XY:

0.446

AC XY:

324107

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.638

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.747

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.503

AC:

76521

AN:

152088

Hom.:

20258

Cov.:

AF XY:

0.505

AC XY:

37504

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.462

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.507

Gnomad4 FIN

AF:

0.390

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.467

Hom.:

4849

Bravo

AF:

0.522

Asia WGS

AF:

0.615

AC:

2137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Surfactant metabolism dysfunction, pulmonary, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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