rs323017

Positions:

• chr16-2289713-T-C

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.2514-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,385,274 control chromosomes in the GnomAD database, including 23,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2033 hom., cov: 33)
  • Exomes 𝑓: 0.18 (21096 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.360

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=-1.01).
• BP6: Variant 16-2289713-T-C is Benign according to our data. Variant chr16-2289713-T-C is described in ClinVar as [Benign]. Clinvar id is 1280711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.2514-93A>G		intron_variant		ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.2514-93A>G		intron_variant		1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.2340-93A>G		intron_variant		1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.3077-93A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23676 AN: 152064 Hom.: 2030 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.178 AC: 219335 AN: 1233092 Hom.: 21096 AF XY: 0.175 AC XY: 106369 AN XY: 608436

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0880

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0271

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.156 AC: 23690 AN: 152182 Hom.: 2033 Cov.: 33 AF XY: 0.154 AC XY: 11486 AN XY: 74410

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.163

Alfa AF: 0.172 Hom.: 593

Bravo AF: 0.151

Asia WGS AF: 0.0570 AC: 198 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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.17

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: rs323017; hg19: chr16-2339714;