16-2308312-C-T

Variant names:

• chr16-2308312-C-T
• rs323074
• NM_001089.3:c.1285+138G>A

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.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
• Publications: 5 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=-0.87).
• BP6: Variant 16-2308312-C-T is Benign according to our data. Variant chr16-2308312-C-T is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.1285+138G>A		intron_variant	Intron 11 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.1285+138G>A		intron_variant	Intron 11 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.1112-4162G>A		intron_variant	Intron 10 of 31	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.1848+138G>A		intron_variant	Intron 11 of 19	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

African (AFR) AF: 0.0401 AC: 881 AN: 21968

American (AMR) AF: 0.0816 AC: 2834 AN: 34746

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3771 AN: 21252

East Asian (EAS) AF: 0.0269 AC: 892 AN: 33176

South Asian (SAS) AF: 0.0737 AC: 5061 AN: 68648

European-Finnish (FIN) AF: 0.207 AC: 8032 AN: 38862

Middle Eastern (MID) AF: 0.156 AC: 651 AN: 4178

European-Non Finnish (NFE) AF: 0.190 AC: 118128 AN: 621862

Other (OTH) AF: 0.160 AC: 6556 AN: 40928

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

African (AFR) AF: 0.0422 AC: 1753 AN: 41572

American (AMR) AF: 0.119 AC: 1814 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5178

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4828

European-Finnish (FIN) AF: 0.203 AC: 2148 AN: 10596

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12750 AN: 68002

Other (OTH) AF: 0.142 AC: 300 AN: 2108

Alfa AF: 0.129 Hom.: 479

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

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	-0.87
CADD	Benign	5.1
DANN	Benign	0.55
PhyloP100		-0.073
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: rs323074; hg19: chr16-2358313;