16-2299370-T-C

Variant names:

• chr16-2299370-T-C
• rs170447
• NM_001089.3:c.1741+33A>G

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.1741+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,611,130 control chromosomes in the GnomAD database, including 207,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16323 hom., cov: 32)
  • Exomes 𝑓: 0.51 (191290 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.54
• Publications: 14 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=-0.91).
• BP6: Variant 16-2299370-T-C is Benign according to our data. Variant chr16-2299370-T-C is described in ClinVar as Benign. ClinVar VariationId is 1185446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.1741+33A>G		intron_variant	Intron 14 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.1741+33A>G		intron_variant	Intron 14 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.1567+33A>G		intron_variant	Intron 13 of 31	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.2304+33A>G		intron_variant	Intron 14 of 19	1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68394 AN: 151846 Hom.: 16298 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.481

GnomAD2 exomes AF: 0.507 AC: 126243 AN: 248760 AF XY: 0.504

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.551

Gnomad FIN exome AF: 0.555

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.509 AC: 743207 AN: 1459166 Hom.: 191290 Cov.: 46 AF XY: 0.507 AC XY: 368089 AN XY: 726056

African (AFR) AF: 0.271 AC: 9081 AN: 33470

American (AMR) AF: 0.583 AC: 26055 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 12040 AN: 26106

East Asian (EAS) AF: 0.554 AC: 21999 AN: 39684

South Asian (SAS) AF: 0.456 AC: 39325 AN: 86250

European-Finnish (FIN) AF: 0.557 AC: 28671 AN: 51450

Middle Eastern (MID) AF: 0.431 AC: 2485 AN: 5764

European-Non Finnish (NFE) AF: 0.517 AC: 574060 AN: 1111416

Other (OTH) AF: 0.489 AC: 29491 AN: 60350

GnomAD4 genome AF: 0.450 AC: 68456 AN: 151964 Hom.: 16323 Cov.: 32 AF XY: 0.455 AC XY: 33839 AN XY: 74292

African (AFR) AF: 0.283 AC: 11742 AN: 41464

American (AMR) AF: 0.536 AC: 8189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3468

East Asian (EAS) AF: 0.543 AC: 2779 AN: 5114

South Asian (SAS) AF: 0.448 AC: 2156 AN: 4816

European-Finnish (FIN) AF: 0.564 AC: 5980 AN: 10598

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34492 AN: 67896

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.467 Hom.: 3296

Bravo AF: 0.446

Asia WGS AF: 0.457 AC: 1588 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Interstitial lung disease due to ABCA3 deficiency Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.18
PhyloP100		-2.5
Mutation Taster		=97/3	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: rs170447; hg19: chr16-2349371; COSMIC: COSV57060399;