chr16-2317423-G-A

Variant names:

• chr16-2317423-G-A
• rs13332547
• NM_001089.3:c.991-20C>T

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.991-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,662 control chromosomes in the GnomAD database, including 16,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1712 hom., cov: 31)
  • Exomes 𝑓: 0.12 (14954 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.113
• Publications: 9 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=-0.88).
• BP6: Variant 16-2317423-G-A is Benign according to our data. Variant chr16-2317423-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 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.991-20C>T		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.991-20C>T		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.991-20C>T		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.1554-20C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19345 AN: 151948 Hom.: 1699 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.172 AC: 43008 AN: 249976 AF XY: 0.162

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.378

Gnomad FIN exome AF: 0.0946

Gnomad NFE exome AF: 0.0958

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.121 AC: 177303 AN: 1460596 Hom.: 14954 Cov.: 33 AF XY: 0.121 AC XY: 88071 AN XY: 726570

African (AFR) AF: 0.101 AC: 3377 AN: 33472

American (AMR) AF: 0.394 AC: 17624 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2975 AN: 26126

East Asian (EAS) AF: 0.392 AC: 15558 AN: 39690

South Asian (SAS) AF: 0.174 AC: 15036 AN: 86230

European-Finnish (FIN) AF: 0.0916 AC: 4799 AN: 52398

Middle Eastern (MID) AF: 0.119 AC: 687 AN: 5766

European-Non Finnish (NFE) AF: 0.0986 AC: 109662 AN: 1111820

Other (OTH) AF: 0.126 AC: 7585 AN: 60378

GnomAD4 genome AF: 0.128 AC: 19400 AN: 152066 Hom.: 1712 Cov.: 31 AF XY: 0.134 AC XY: 9982 AN XY: 74336

African (AFR) AF: 0.104 AC: 4318 AN: 41504

American (AMR) AF: 0.274 AC: 4179 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1911 AN: 5124

South Asian (SAS) AF: 0.176 AC: 846 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10596

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.0926 AC: 6293 AN: 67970

Other (OTH) AF: 0.137 AC: 290 AN: 2116

Alfa AF: 0.105 Hom.: 208

Bravo AF: 0.142

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hereditary pulmonary alveolar proteinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.36
PhyloP100		-0.11
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: rs13332547; hg19: chr16-2367424; COSMIC: COSV57055826;