16-2314050-C-G

Variant names:

• chr16-2314050-C-G
• rs323069
• NM_001089.3:c.1111+3233G>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.1111+3233G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,966 control chromosomes in the GnomAD database, including 6,712 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 0.29 (6712 hom., cov: 31)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 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: ClinGen, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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.1111+3233G>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.1111+3233G>C		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.1111+3233G>C		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.1674+3233G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44332 AN: 151848 Hom.: 6696 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.292 AC: 44380 AN: 151966 Hom.: 6712 Cov.: 31 AF XY: 0.297 AC XY: 22050 AN XY: 74258

African (AFR) AF: 0.242 AC: 10042 AN: 41450

American (AMR) AF: 0.408 AC: 6226 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1021 AN: 3466

East Asian (EAS) AF: 0.409 AC: 2112 AN: 5168

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4810

European-Finnish (FIN) AF: 0.318 AC: 3349 AN: 10544

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19493 AN: 67952

Other (OTH) AF: 0.302 AC: 638 AN: 2110

Alfa AF: 0.285 Hom.: 806

Bravo AF: 0.303

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.14
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: rs323069; hg19: chr16-2364051;