16-2298656-A-G

Position:

• chr16-2298656-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.1742-116T>C		intron_variant		ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.1742-116T>C		intron_variant		1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.1568-116T>C		intron_variant		1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.2305-116T>C		intron_variant		1

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

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.430

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.412

Alfa AF: 0.285 Hom.: 793

Bravo AF: 0.427

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240523; hg19: chr16-2348657; COSMIC: COSV57050800;