16-2289713-T-G

Variant names:

• chr16-2289713-T-G
• rs323017
• NM_001089.3:c.2514-93A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001089.3(ABCA3):​c.2514-93A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000081 in 1,234,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 0 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: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.2514-93A>C		intron_variant	Intron 19 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.2514-93A>C		intron_variant	Intron 19 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.2340-93A>C		intron_variant	Intron 18 of 31	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.3077-93A>C		intron_variant	Intron 19 of 19	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.10e-7 AC: 1 AN: 1234508 Hom.: 0 AF XY: 0.00000164 AC XY: 1 AN XY: 609144

African (AFR) AF: 0.00 AC: 0 AN: 28396

American (AMR) AF: 0.00 AC: 0 AN: 33806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23448

East Asian (EAS) AF: 0.0000290 AC: 1 AN: 34454

South Asian (SAS) AF: 0.00 AC: 0 AN: 74332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949304

Other (OTH) AF: 0.00 AC: 0 AN: 52296

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.24
PhyloP100		-0.36

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: rs323017; hg19: chr16-2339714;