16-2281429-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001089.3(ABCA3):c.4116T>C(p.Ser1372Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,613,668 control chromosomes in the GnomAD database, including 674,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59447 hom., cov: 32)

Exomes 𝑓: 0.92 ( 614736 hom. )

Consequence

ABCA3
NM_001089.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.158

Publications

24 publications found

Variant links:

Genes affected

ABCA3 (HGNC:33): (ATP binding cassette subfamily A member 3) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]

ABCA3 Gene-Disease associations (from GenCC):

interstitial lung disease due to ABCA3 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ABCA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-2281429-A-G is Benign according to our data. Variant chr16-2281429-A-G is described in ClinVar as Benign. ClinVar VariationId is 162672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001089.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	NM_001089.3	MANE Select	c.4116T>C	p.Ser1372Ser	synonymous	Exon 27 of 33	NP_001080.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.4116T>C	p.Ser1372Ser	synonymous	Exon 27 of 33	ENSP00000301732.5
ABCA3	ENST00000382381.7	TSL:1	c.3942T>C	p.Ser1314Ser	synonymous	Exon 26 of 32	ENSP00000371818.3
ABCA3	ENST00000566200.1	TSL:3	n.637T>C		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

134071

AN:

152130

Hom.:

59400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.977

Gnomad AMR

AF:

0.914

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.957

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.893

GnomAD2 exomes

AF:

0.923

AC:

231790

AN:

251228

AF XY:

0.924

show subpopulations

Gnomad AFR exome

AF:

0.778

Gnomad AMR exome

AF:

0.943

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.958

Gnomad NFE exome

AF:

0.911

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.917

AC:

1339502

AN:

1461420

Hom.:

614736

Cov.:

AF XY:

0.918

AC XY:

667028

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.773

AC:

25876

AN:

33480

American (AMR)

AF:

0.941

AC:

42063

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

23796

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39692

AN:

39700

South Asian (SAS)

AF:

0.953

AC:

82224

AN:

86258

European-Finnish (FIN)

AF:

0.956

AC:

50699

AN:

53006

Middle Eastern (MID)

AF:

0.884

AC:

5100

AN:

5768

European-Non Finnish (NFE)

AF:

0.913

AC:

1015052

AN:

1111968

Other (OTH)

AF:

0.911

AC:

55000

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7643

15285

22928

30570

38213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21502

43004

64506

86008

107510

<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:

0.881

AC:

134172

AN:

152248

Hom.:

59447

Cov.:

AF XY:

0.886

AC XY:

65964

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.774

AC:

32139

AN:

41504

American (AMR)

AF:

0.915

AC:

13987

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3138

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5175

AN:

5180

South Asian (SAS)

AF:

0.952

AC:

4598

AN:

4828

European-Finnish (FIN)

AF:

0.957

AC:

10172

AN:

10628

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.910

AC:

61916

AN:

68024

Other (OTH)

AF:

0.894

AC:

1888

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

791

1582

2372

3163

3954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<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:

0.888

Hom.:

110285

Bravo

AF:

0.874

Asia WGS

AF:

0.966

AC:

3360

AN:

3478

EpiCase

AF:

0.903

EpiControl

AF:

0.902

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser1372Ser in exon 27 of ABCA3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 22.0% (968/4396) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs149532).

Interstitial lung disease due to ABCA3 deficiency

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.8

(source)

DANN

Benign

0.42

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over