chr16-2323686-C-T

Variant names:

• chr16-2323686-C-T
• rs74002800
• NM_001089.3:c.450G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001089.3(ABCA3):​c.450G>A​(p.Val150Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,614,074 control chromosomes in the GnomAD database, including 575 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (302 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (273 hom.)
• Consequence: ABCA3 NM_001089.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0740
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 16-2323686-C-T is Benign according to our data. Variant chr16-2323686-C-T is described in ClinVar as Benign. ClinVar VariationId is 178701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.450G>A	p.Val150Val	splice_region synonymous	Exon 7 of 33	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.450G>A	p.Val150Val	splice_region synonymous	Exon 7 of 33	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.450G>A	p.Val150Val	splice_region synonymous	Exon 7 of 32	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000567910.1	TSL:1	c.450G>A	p.Val150Val	splice_region synonymous	Exon 6 of 6	ENSP00000454397.1	Q99758-2

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5166 AN: 152138 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.00892 AC: 2244 AN: 251476 AF XY: 0.00636

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.00668

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000360

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00368 AC: 5377 AN: 1461818 Hom.: 273 Cov.: 31 AF XY: 0.00312 AC XY: 2268 AN XY: 727210

African (AFR) AF: 0.125 AC: 4194 AN: 33474

American (AMR) AF: 0.00749 AC: 335 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.000263 AC: 293 AN: 1111972

Other (OTH) AF: 0.00808 AC: 488 AN: 60382

GnomAD4 genome AF: 0.0340 AC: 5179 AN: 152256 Hom.: 302 Cov.: 32 AF XY: 0.0331 AC XY: 2465 AN XY: 74454

African (AFR) AF: 0.118 AC: 4895 AN: 41500

American (AMR) AF: 0.0124 AC: 190 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68034

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0163 Hom.: 127

Bravo AF: 0.0400

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000593

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)
-	-	1	Interstitial lung disease due to ABCA3 deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.0
DANN	Benign	0.79
PhyloP100		-0.074
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs74002800; hg19: chr16-2373687;