rs45480502

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001089.3(ABCA3):c.681C>T(p.Ala227Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,613,952 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A227A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 34 hom., cov: 30)

Exomes 𝑓: 0.021 ( 378 hom. )

Consequence

ABCA3
NM_001089.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.370

Publications

7 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen

ABCA3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001089.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.9).

BP6

Variant 16-2319773-G-A is Benign according to our data. Variant chr16-2319773-G-A is described in ClinVar as Benign. ClinVar VariationId is 162673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.37 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0165 (2516/152160) while in subpopulation SAS AF = 0.0214 (103/4816). AF 95% confidence interval is 0.0201. There are 34 homozygotes in GnomAd4. There are 1284 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	NM_001089.3	MANE Select	c.681C>T	p.Ala227Ala	synonymous	Exon 8 of 33	NP_001080.2	Q99758-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.681C>T	p.Ala227Ala	synonymous	Exon 8 of 33	ENSP00000301732.5	Q99758-1
ABCA3	ENST00000382381.7	TSL:1	c.681C>T	p.Ala227Ala	synonymous	Exon 8 of 32	ENSP00000371818.3	H0Y3H2
ABCA3	ENST00000563623.5	TSL:1	n.1244C>T		non_coding_transcript_exon	Exon 8 of 20

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2514

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.0518

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0185

AC:

4641

AN:

251126

AF XY:

0.0199

show subpopulations

Gnomad AFR exome

AF:

0.00333

Gnomad AMR exome

AF:

0.00633

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0226

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0214

AC:

31283

AN:

1461792

Hom.:

378

Cov.:

AF XY:

0.0216

AC XY:

15715

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

33480

American (AMR)

AF:

0.00756

AC:

338

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

610

AN:

26136

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.0211

AC:

1818

AN:

86258

European-Finnish (FIN)

AF:

0.0371

AC:

1977

AN:

53322

Middle Eastern (MID)

AF:

0.0272

AC:

157

AN:

5768

European-Non Finnish (NFE)

AF:

0.0225

AC:

25014

AN:

1112010

Other (OTH)

AF:

0.0209

AC:

1262

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2099

4199

6298

8398

10497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

948

1896

2844

3792

4740

<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:

0.0165

AC:

2516

AN:

152160

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1284

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41538

American (AMR)

AF:

0.0161

AC:

246

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5170

South Asian (SAS)

AF:

0.0214

AC:

103

AN:

4816

European-Finnish (FIN)

AF:

0.0402

AC:

426

AN:

10584

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0210

AC:

1430

AN:

68000

Other (OTH)

AF:

0.0165

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0189

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0201

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hereditary pulmonary alveolar proteinosis (1)

Interstitial lung disease due to ABCA3 deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.92

(source)

DANN

Benign

0.53

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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