chr16-2280168-C-G

Variant names:

• chr16-2280168-C-G
• rs150926
• NM_001089.3:c.4359+859G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001089.3(ABCA3):​c.4359+859G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,164 control chromosomes in the GnomAD database, including 14,655 homozygotes. 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: 𝑓 0.44 (14655 hom., cov: 33)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.4359+859G>C		intron_variant	Intron 28 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.4359+859G>C		intron_variant	Intron 28 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.4185+859G>C		intron_variant	Intron 27 of 31	1		ENSP00000371818.3
ABCA3	ENST00000566200.1	n.880+859G>C		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66260 AN: 152046 Hom.: 14650 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.436 AC: 66289 AN: 152164 Hom.: 14655 Cov.: 33 AF XY: 0.435 AC XY: 32363 AN XY: 74394

African (AFR) AF: 0.493 AC: 20450 AN: 41514

American (AMR) AF: 0.386 AC: 5904 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3472

East Asian (EAS) AF: 0.518 AC: 2682 AN: 5180

South Asian (SAS) AF: 0.513 AC: 2476 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4159 AN: 10600

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27501 AN: 67962

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.418 Hom.: 1884

Bravo AF: 0.434

Asia WGS AF: 0.531 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.45
PhyloP100		-1.1
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: rs150926; hg19: chr16-2330169;