Variant 8-22161907-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001317778.2(SFTPC):c.42+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,600,204 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 46 hom. )

Consequence

SFTPC
NM_001317778.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.516

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-22161907-G-A is Benign according to our data. Variant chr8-22161907-G-A is described in ClinVar as [Benign]. Clinvar id is 1283058.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00257 (391/152254) while in subpopulation EAS AF= 0.0472 (243/5152). AF 95% confidence interval is 0.0423. There are 8 homozygotes in gnomad4. There are 231 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPC	NM_001317778.2 linkuse as main transcript	c.42+37G>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.42+37G>A		intron_variant			NM_001317778.2	A1

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0471

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00487

AC:

1203

AN:

247172

Hom.:

AF XY:

0.00464

AC XY:

623

AN XY:

134202

show subpopulations

Gnomad AFR exome

AF:

0.000518

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.0506

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00398

Gnomad NFE exome

AF:

0.000483

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00192

AC:

2775

AN:

1447950

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1408

AN XY:

721060

show subpopulations

Gnomad4 AFR exome

AF:

0.000482

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00438

Gnomad4 EAS exome

AF:

0.0417

Gnomad4 SAS exome

AF:

0.00237

Gnomad4 FIN exome

AF:

0.00360

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.00257

AC:

391

AN:

152254

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.58

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