rs185179294

Variant names:

• chr16-2317634-G-A
• rs185179294
• NM_001089.3:c.990+14C>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.990+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,728 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (336 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.482
• 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: 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=-0.86).
• BP6: Variant 16-2317634-G-A is Benign according to our data. Variant chr16-2317634-G-A is described in ClinVar as Benign. ClinVar VariationId is 226454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0824 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.990+14C>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.990+14C>T		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.990+14C>T		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.1553+14C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00922 AC: 1403 AN: 152218 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0172 AC: 4312 AN: 251312 AF XY: 0.0129

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00239

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00390 AC: 5696 AN: 1461392 Hom.: 336 Cov.: 32 AF XY: 0.00331 AC XY: 2405 AN XY: 727026

African (AFR) AF: 0.000777 AC: 26 AN: 33460

American (AMR) AF: 0.115 AC: 5133 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00665 AC: 264 AN: 39696

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86206

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111630

Other (OTH) AF: 0.00338 AC: 204 AN: 60378

GnomAD4 genome AF: 0.00929 AC: 1415 AN: 152336 Hom.: 63 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74496

African (AFR) AF: 0.00125 AC: 52 AN: 41586

American (AMR) AF: 0.0862 AC: 1320 AN: 15308

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

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00372 Hom.: 6

Bravo AF: 0.0157

Asia WGS AF: 0.00577 AC: 20 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)
-	-	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	-0.86
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.48
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: rs185179294; hg19: chr16-2367635; COSMIC: COSV57060408;