rs313909

Positions:

• chr16-2287992-G-A
• chr16-2287992-G-C
• chr16-2287992-G-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.3004+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,594,848 control chromosomes in the GnomAD database, including 135,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14400 hom., cov: 32)
  • Exomes 𝑓: 0.41 (120782 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-2287992-G-A is Benign according to our data. Variant chr16-2287992-G-A is described in ClinVar as [Benign]. Clinvar id is 1290757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.3004+34C>T		intron_variant		ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.3004+34C>T		intron_variant		1	NM_001089.3	ENSP00000301732	P1
ABCA3	ENST00000382381.7	c.2830+34C>T		intron_variant		1		ENSP00000371818

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65649 AN: 151948 Hom.: 14391 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.415

GnomAD3 exomes AF: 0.415 AC: 95750 AN: 230630 Hom.: 20274 AF XY: 0.420 AC XY: 53523 AN XY: 127328

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.494

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.407 AC: 586657 AN: 1442784 Hom.: 120782 Cov.: 39 AF XY: 0.410 AC XY: 294231 AN XY: 717762

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.432 AC: 65685 AN: 152064 Hom.: 14400 Cov.: 32 AF XY: 0.431 AC XY: 32035 AN XY: 74324

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.419

Alfa AF: 0.367 Hom.: 2659

Bravo AF: 0.430

Asia WGS AF: 0.502 AC: 1745 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	-0.92
CADD	Benign	1.3
DANN	Benign	0.47

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: rs313909; hg19: chr16-2337993;