rs149532

Variant names:

• chr16-2281429-A-G
• rs149532
• NM_001089.3:c.4116T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2281429-A-G
• chr16-2281429-A-C
• chr16-2281429-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.158
• Publications: 24 publications found

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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

Sel.	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	Q99758-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.4116T>C	p.Ser1372Ser	synonymous	Exon 27 of 33	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.3942T>C	p.Ser1314Ser	synonymous	Exon 26 of 32	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000967440.1		c.4116T>C	p.Ser1372Ser	synonymous	Exon 27 of 33	ENSP00000637499.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134071 AN: 152130 Hom.: 59400 Cov.: 32

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

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.: 70 AF XY: 0.918 AC XY: 667028 AN XY: 726992

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

GnomAD4 genome AF: 0.881 AC: 134172 AN: 152248 Hom.: 59447 Cov.: 32 AF XY: 0.886 AC XY: 65964 AN XY: 74480

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Interstitial lung disease due to ABCA3 deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs149532; hg19: chr16-2331430; COSMIC: COSV57057418;