chr16-2284553-A-T

Variant names:

• chr16-2284553-A-T
• rs1183064
• NM_001089.3:c.3704-116T>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.3704-116T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,453,402 control chromosomes in the GnomAD database, including 397,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38042 hom., cov: 32)
  • Exomes 𝑓: 0.74 (359000 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.87
• Publications: 6 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=-0.93).
• BP6: Variant 16-2284553-A-T is Benign according to our data. Variant chr16-2284553-A-T is described in ClinVar as Benign. ClinVar VariationId is 1270540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 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.3704-116T>A		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.3704-116T>A		intron	N/A	ENSP00000301732.5
	ABCA3	ENST00000382381.7	TSL:1	c.3530-116T>A		intron	N/A	ENSP00000371818.3

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106318 AN: 151814 Hom.: 38011 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.739 AC: 961531 AN: 1301470 Hom.: 359000 AF XY: 0.743 AC XY: 485208 AN XY: 652998

African (AFR) AF: 0.562 AC: 16955 AN: 30144

American (AMR) AF: 0.854 AC: 36520 AN: 42788

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 17796 AN: 24978

East Asian (EAS) AF: 0.973 AC: 37498 AN: 38552

South Asian (SAS) AF: 0.875 AC: 71811 AN: 82100

European-Finnish (FIN) AF: 0.751 AC: 38048 AN: 50640

Middle Eastern (MID) AF: 0.699 AC: 2791 AN: 3990

European-Non Finnish (NFE) AF: 0.719 AC: 699825 AN: 973456

Other (OTH) AF: 0.735 AC: 40287 AN: 54822

GnomAD4 genome AF: 0.700 AC: 106392 AN: 151932 Hom.: 38042 Cov.: 32 AF XY: 0.707 AC XY: 52494 AN XY: 74264

African (AFR) AF: 0.566 AC: 23441 AN: 41422

American (AMR) AF: 0.783 AC: 11952 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2468 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5001 AN: 5124

South Asian (SAS) AF: 0.877 AC: 4230 AN: 4824

European-Finnish (FIN) AF: 0.754 AC: 7982 AN: 10580

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48881 AN: 67926

Other (OTH) AF: 0.715 AC: 1508 AN: 2110

Alfa AF: 0.700 Hom.: 4466

Bravo AF: 0.694

Asia WGS AF: 0.901 AC: 3132 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	-0.93
CADD	Benign	0.82
DANN	Benign	0.68
PhyloP100		-4.9
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: rs1183064; hg19: chr16-2334554; COSMIC: COSV57057572; COSMIC: COSV57057572;