16-2286393-T-C

Variant names:

• chr16-2286393-T-C
• rs2014467
• NM_001089.3:c.3278+301A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001089.3(ABCA3):​c.3278+301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,102 control chromosomes in the GnomAD database, including 6,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6958 hom., cov: 32)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.37
• Publications: 20 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-2286393-T-C is Benign according to our data. Variant chr16-2286393-T-C is described in ClinVar as Benign. ClinVar VariationId is 1262016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 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.3278+301A>G		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.3278+301A>G		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.3104+301A>G		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000967440.1		c.3278+301A>G		intron	N/A	ENSP00000637499.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40773 AN: 151984 Hom.: 6945 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40799 AN: 152102 Hom.: 6958 Cov.: 32 AF XY: 0.276 AC XY: 20555 AN XY: 74358

African (AFR) AF: 0.0640 AC: 2656 AN: 41508

American (AMR) AF: 0.396 AC: 6047 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2696 AN: 5164

South Asian (SAS) AF: 0.364 AC: 1757 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4059 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21761 AN: 67968

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.318 Hom.: 5371

Bravo AF: 0.263

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.052
DANN	Benign	0.36
PhyloP100		-3.4
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: rs2014467; hg19: chr16-2336394;