rs2240523

Variant names:

• chr16-2298656-A-G
• rs2240523
• NM_001089.3:c.1742-116T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2298656-A-G
• chr16-2298656-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001089.3(ABCA3):​c.1742-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,308,700 control chromosomes in the GnomAD database, including 115,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14147 hom., cov: 29)
  • Exomes 𝑓: 0.42 (101040 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.03
• Publications: 8 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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 16-2298656-A-G is Benign according to our data. Variant chr16-2298656-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 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.1742-116T>C		intron	N/A	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.1742-116T>C		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.1568-116T>C		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.2305-116T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65043 AN: 151132 Hom.: 14140 Cov.: 29

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.416 AC: 481663 AN: 1157452 Hom.: 101040 AF XY: 0.420 AC XY: 243519 AN XY: 580050

African (AFR) AF: 0.495 AC: 13562 AN: 27424

American (AMR) AF: 0.363 AC: 12905 AN: 35554

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 10128 AN: 22468

East Asian (EAS) AF: 0.454 AC: 15952 AN: 35154

South Asian (SAS) AF: 0.510 AC: 38054 AN: 74550

European-Finnish (FIN) AF: 0.397 AC: 13680 AN: 34444

Middle Eastern (MID) AF: 0.456 AC: 1620 AN: 3556

European-Non Finnish (NFE) AF: 0.405 AC: 354275 AN: 874308

Other (OTH) AF: 0.430 AC: 21487 AN: 49994

GnomAD4 genome AF: 0.430 AC: 65079 AN: 151248 Hom.: 14147 Cov.: 29 AF XY: 0.430 AC XY: 31745 AN XY: 73840

African (AFR) AF: 0.483 AC: 19921 AN: 41230

American (AMR) AF: 0.382 AC: 5806 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1590 AN: 3462

East Asian (EAS) AF: 0.468 AC: 2385 AN: 5096

South Asian (SAS) AF: 0.515 AC: 2463 AN: 4786

European-Finnish (FIN) AF: 0.395 AC: 4130 AN: 10450

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27317 AN: 67742

Other (OTH) AF: 0.412 AC: 866 AN: 2100

Alfa AF: 0.296 Hom.: 891

Bravo AF: 0.427

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.15
PhyloP100		-4.0
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

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

Other links and lift over

dbSNP: rs2240523;

hg19: chr16-2348657;

COSMIC: COSV57050800;