16-2288362-C-G

Variant names:

• chr16-2288362-C-G
• rs313908
• NM_001089.3:c.2701-33G>C

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.2701-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,534,392 control chromosomes in the GnomAD database, including 423,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38880 hom., cov: 33)
  • Exomes 𝑓: 0.74 (384615 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.184

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-2288362-C-G is Benign according to our data. Variant chr16-2288362-C-G is described in ClinVar as [Benign]. Clinvar id is 1185445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.2701-33G>C		intron_variant	Intron 20 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.2701-33G>C		intron_variant	Intron 20 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.2527-33G>C		intron_variant	Intron 19 of 31	1		ENSP00000371818.3

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107459 AN: 152034 Hom.: 38852 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.789 AC: 110093 AN: 139536 AF XY: 0.792

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.716

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.743 AC: 1026806 AN: 1382240 Hom.: 384615 Cov.: 45 AF XY: 0.747 AC XY: 509046 AN XY: 681676

Gnomad4 AFR exome AF: 0.560 AC: 17697 AN: 31604

Gnomad4 AMR exome AF: 0.847 AC: 30254 AN: 35728

Gnomad4 ASJ exome AF: 0.715 AC: 17970 AN: 25118

Gnomad4 EAS exome AF: 0.973 AC: 34802 AN: 35776

Gnomad4 SAS exome AF: 0.874 AC: 69180 AN: 79110

Gnomad4 FIN exome AF: 0.784 AC: 27113 AN: 34566

Gnomad4 NFE exome AF: 0.727 AC: 783133 AN: 1077072

Gnomad4 Remaining exome AF: 0.740 AC: 42776 AN: 57782

GnomAD4 genome AF: 0.707 AC: 107530 AN: 152152 Hom.: 38880 Cov.: 33 AF XY: 0.715 AC XY: 53191 AN XY: 74390

Gnomad4 AFR AF: 0.563 AC: 0.563352 AN: 0.563352

Gnomad4 AMR AF: 0.784 AC: 0.784005 AN: 0.784005

Gnomad4 ASJ AF: 0.715 AC: 0.71515 AN: 0.71515

Gnomad4 EAS AF: 0.976 AC: 0.976218 AN: 0.976218

Gnomad4 SAS AF: 0.877 AC: 0.87728 AN: 0.87728

Gnomad4 FIN AF: 0.798 AC: 0.797509 AN: 0.797509

Gnomad4 NFE AF: 0.728 AC: 0.728206 AN: 0.728206

Gnomad4 OTH AF: 0.718 AC: 0.718336 AN: 0.718336

Alfa AF: 0.682 Hom.: 4557

Bravo AF: 0.697

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 21, 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	-0.84
CADD	Benign	0.23
DANN	Benign	0.38
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

Publications

LitVar

Other links and lift over

dbSNP: rs313908; hg19: chr16-2338363;