rs323017

Variant names:

• chr16-2289713-T-C
• rs323017
• NM_001089.3:c.2514-93A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2289713-T-C
• chr16-2289713-T-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.2514-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,385,274 control chromosomes in the GnomAD database, including 23,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2033 hom., cov: 33)
  • Exomes 𝑓: 0.18 (21096 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.360
• Publications: 4 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, 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=-1.01).
• BP6: Variant 16-2289713-T-C is Benign according to our data. Variant chr16-2289713-T-C is described in ClinVar as Benign. ClinVar VariationId is 1280711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	NM_001089.3	MANE Select	c.2514-93A>G		intron	N/A	NP_001080.2	Q99758-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA3	ENST00000301732.10	TSL:1 MANE Select	c.2514-93A>G		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.2340-93A>G		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.3077-93A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23676 AN: 152064 Hom.: 2030 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.178 AC: 219335 AN: 1233092 Hom.: 21096 AF XY: 0.175 AC XY: 106369 AN XY: 608436

African (AFR) AF: 0.115 AC: 3251 AN: 28370

American (AMR) AF: 0.0880 AC: 2974 AN: 33794

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4680 AN: 23430

East Asian (EAS) AF: 0.0271 AC: 933 AN: 34454

South Asian (SAS) AF: 0.0806 AC: 5992 AN: 74306

European-Finnish (FIN) AF: 0.207 AC: 7111 AN: 34312

Middle Eastern (MID) AF: 0.168 AC: 696 AN: 4140

European-Non Finnish (NFE) AF: 0.195 AC: 184834 AN: 948048

Other (OTH) AF: 0.170 AC: 8864 AN: 52238

GnomAD4 genome AF: 0.156 AC: 23690 AN: 152182 Hom.: 2033 Cov.: 33 AF XY: 0.154 AC XY: 11486 AN XY: 74410

African (AFR) AF: 0.116 AC: 4822 AN: 41526

American (AMR) AF: 0.128 AC: 1952 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3472

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5178

South Asian (SAS) AF: 0.0775 AC: 374 AN: 4828

European-Finnish (FIN) AF: 0.204 AC: 2162 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13016 AN: 67982

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.170 Hom.: 598

Bravo AF: 0.151

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.17
PhyloP100		-0.36
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: rs323017; hg19: chr16-2339714;