rs45502600

Variant names:

• chr16-2289628-G-A
• rs45502600
• NM_001089.3:c.2514-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2289628-G-A
• chr16-2289628-G-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.2514-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,548,062 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (131 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (128 hom.)
• Consequence: ABCA3 NM_001089.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002179
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.148
• Publications: 1 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=-0.84).
• BP6: Variant 16-2289628-G-A is Benign according to our data. Variant chr16-2289628-G-A is described in ClinVar as Benign. ClinVar VariationId is 226452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.2514-8C>T		splice_region_variant, intron_variant	Intron 19 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.2514-8C>T		splice_region_variant, intron_variant	Intron 19 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.2340-8C>T		splice_region_variant, intron_variant	Intron 18 of 31	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.3077-8C>T		splice_region_variant, intron_variant	Intron 19 of 19	1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3403 AN: 152218 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00613 AC: 938 AN: 152910 AF XY: 0.00483

Gnomad AFR exome AF: 0.0781

Gnomad AMR exome AF: 0.00643

Gnomad ASJ exome AF: 0.00106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00122

Gnomad OTH exome AF: 0.00411

GnomAD4 exome AF: 0.00273 AC: 3808 AN: 1395726 Hom.: 128 Cov.: 36 AF XY: 0.00246 AC XY: 1694 AN XY: 688558

African (AFR) AF: 0.0800 AC: 2531 AN: 31626

American (AMR) AF: 0.00658 AC: 235 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 26 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35838

South Asian (SAS) AF: 0.000290 AC: 23 AN: 79188

European-Finnish (FIN) AF: 0.0000432 AC: 2 AN: 46336

Middle Eastern (MID) AF: 0.00721 AC: 35 AN: 4856

European-Non Finnish (NFE) AF: 0.000525 AC: 567 AN: 1079076

Other (OTH) AF: 0.00672 AC: 389 AN: 57898

GnomAD4 genome AF: 0.0224 AC: 3411 AN: 152336 Hom.: 131 Cov.: 33 AF XY: 0.0217 AC XY: 1620 AN XY: 74496

African (AFR) AF: 0.0763 AC: 3170 AN: 41570

American (AMR) AF: 0.00810 AC: 124 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68030

Other (OTH) AF: 0.0199 AC: 42 AN: 2108

Alfa AF: 0.00815 Hom.: 13

Bravo AF: 0.0256

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2514-8C>T in intron 19 of ABCA3: This variant is not expected to have clinical s ignificance because it has been identified in 6.5% (280/4282) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs45502600). -

Interstitial lung disease due to ABCA3 deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.39
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0040
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: rs45502600; hg19: chr16-2339629;