16-2308312-C-T

Position:

• chr16-2308312-C-T

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.1285+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,037,866 control chromosomes in the GnomAD database, including 15,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1696 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13861 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730

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=-0.87).
• BP6: Variant 16-2308312-C-T is Benign according to our data. Variant chr16-2308312-C-T is described in ClinVar as [Benign]. Clinvar id is 1250899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.1285+138G>A		intron_variant		ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.1285+138G>A		intron_variant		1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.1112-4162G>A		intron_variant		1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.1848+138G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20042 AN: 152128 Hom.: 1698 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.166 AC: 146806 AN: 885620 Hom.: 13861 AF XY: 0.163 AC XY: 74106 AN XY: 455856

Gnomad4 AFR exome AF: 0.0401

Gnomad4 AMR exome AF: 0.0816

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.0737

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.132 AC: 20029 AN: 152246 Hom.: 1696 Cov.: 32 AF XY: 0.131 AC XY: 9722 AN XY: 74442

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0704

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0812 Hom.: 161

Bravo AF: 0.124

Asia WGS AF: 0.0460 AC: 161 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	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.55

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: rs323074; hg19: chr16-2358313;