chr16-2287992-G-A

Variant names:

• chr16-2287992-G-A
• rs313909
• NM_001089.3:c.3004+34C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	NM_001089.3	MANE Select	c.3004+34C>T		intron	N/A	NP_001080.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.3004+34C>T		intron	N/A	ENSP00000301732.5
	ABCA3	ENST00000382381.7	TSL:1	c.2830+34C>T		intron	N/A	ENSP00000371818.3

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

GnomAD2 exomes AF: 0.415 AC: 95750 AN: 230630 AF XY: 0.420

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 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

African (AFR) AF: 0.503 AC: 16783 AN: 33362

American (AMR) AF: 0.359 AC: 16019 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 11801 AN: 26088

East Asian (EAS) AF: 0.444 AC: 17583 AN: 39628

South Asian (SAS) AF: 0.496 AC: 42690 AN: 86034

European-Finnish (FIN) AF: 0.395 AC: 15476 AN: 39208

Middle Eastern (MID) AF: 0.455 AC: 1953 AN: 4296

European-Non Finnish (NFE) AF: 0.396 AC: 438968 AN: 1109628

Other (OTH) AF: 0.423 AC: 25384 AN: 59962

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

African (AFR) AF: 0.493 AC: 20465 AN: 41482

American (AMR) AF: 0.384 AC: 5868 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2334 AN: 5162

South Asian (SAS) AF: 0.505 AC: 2433 AN: 4822

European-Finnish (FIN) AF: 0.393 AC: 4151 AN: 10564

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27345 AN: 67968

Other (OTH) AF: 0.419 AC: 885 AN: 2114

Alfa AF: 0.370 Hom.: 2762

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.14
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: rs313909; hg19: chr16-2337993;