Genetic Variant SFTPA1:c.-23-153G>T (chr10-79611650-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005411.5(SFTPA1):c.-23-153G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000727 in 151,392 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00073 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000085 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

SFTPA1
NM_005411.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.964

Publications

1 publications found

Variant links:

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SFTPA1 Gene-Disease associations (from GenCC):

interstitial lung disease 1
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

SFTPA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPA1	NM_005411.5	MANE Select	c.-23-153G>T	intron	N/A	NP_005402.3
SFTPA1	NM_001093770.3		c.22+9G>T	intron	N/A	NP_001087239.2	Q8IWL2-2
SFTPA1	NM_001164644.2		c.-23-153G>T	intron	N/A	NP_001158116.1	Q8IWL2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPA1	ENST00000398636.8	TSL:1 MANE Select	c.-23-153G>T	intron	N/A	ENSP00000381633.3	Q8IWL2-1
SFTPA1	ENST00000419470.6	TSL:1	c.22+9G>T	intron	N/A	ENSP00000397082.2	Q8IWL2-2
SFTPA1	ENST00000428376.6	TSL:1	c.-23-153G>T	intron	N/A	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes

AF:

0.000694

AC:

105

AN:

151268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000964

GnomAD2 exomes

AF:

0.000174

AC:

AN:

166588

AF XY:

0.000158

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.000159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000849

AC:

119

AN:

1402014

Hom.:

Cov.:

AF XY:

0.0000693

AC XY:

AN XY:

692174

show subpopulations

African (AFR)

AF:

0.00186

AC:

AN:

31804

American (AMR)

AF:

0.000223

AC:

AN:

35928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25124

East Asian (EAS)

AF:

0.0000559

AC:

AN:

35800

South Asian (SAS)

AF:

0.0000250

AC:

AN:

79992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49620

Middle Eastern (MID)

AF:

0.000405

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.0000222

AC:

AN:

1080798

Other (OTH)

AF:

0.000379

AC:

AN:

58014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000727

AC:

110

AN:

151392

Hom.:

Cov.:

AF XY:

0.000581

AC XY:

AN XY:

73994

show subpopulations

African (AFR)

AF:

0.00249

AC:

103

AN:

41294

American (AMR)

AF:

0.000197

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5046

South Asian (SAS)

AF:

0.000212

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67742

Other (OTH)

AF:

0.000953

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000182

Hom.:

Bravo

AF:

0.000812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.91

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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