NM_001089.3:c.447+11C>T

Variant names:

• chr16-2324393-G-A
• rs117031141
• NM_001089.3:c.447+11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001089.3(ABCA3):​c.447+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,587,038 control chromosomes in the GnomAD database, including 524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (48 hom., cov: 31)
  • Exomes 𝑓: 0.024 (476 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.19
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-2324393-G-A is Benign according to our data. Variant chr16-2324393-G-A is described in ClinVar as Benign. ClinVar VariationId is 162675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0194 (2961/152286) while in subpopulation NFE AF = 0.0275 (1871/68008). AF 95% confidence interval is 0.0265. There are 48 homozygotes in GnomAd4. There are 1428 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

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.447+11C>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.447+11C>T		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.447+11C>T		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000567910.1	TSL:1	c.447+11C>T		intron	N/A	ENSP00000454397.1	Q99758-2

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2965 AN: 152170 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.0179 AC: 3797 AN: 211748 AF XY: 0.0185

Gnomad AFR exome AF: 0.00408

Gnomad AMR exome AF: 0.00792

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0249

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0238 AC: 34194 AN: 1434752 Hom.: 476 Cov.: 31 AF XY: 0.0236 AC XY: 16812 AN XY: 712548

African (AFR) AF: 0.00362 AC: 120 AN: 33140

American (AMR) AF: 0.00829 AC: 346 AN: 41740

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 689 AN: 25654

East Asian (EAS) AF: 0.0000770 AC: 3 AN: 38986

South Asian (SAS) AF: 0.0120 AC: 1004 AN: 83580

European-Finnish (FIN) AF: 0.0312 AC: 1310 AN: 42000

Middle Eastern (MID) AF: 0.0234 AC: 129 AN: 5508

European-Non Finnish (NFE) AF: 0.0266 AC: 29334 AN: 1104482

Other (OTH) AF: 0.0211 AC: 1259 AN: 59662

GnomAD4 genome AF: 0.0194 AC: 2961 AN: 152286 Hom.: 48 Cov.: 31 AF XY: 0.0192 AC XY: 1428 AN XY: 74468

African (AFR) AF: 0.00462 AC: 192 AN: 41554

American (AMR) AF: 0.0123 AC: 188 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4830

European-Finnish (FIN) AF: 0.0410 AC: 435 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1871 AN: 68008

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.0245 Hom.: 49

Bravo AF: 0.0168

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.85
CADD	Benign	0.18
DANN	Benign	0.56
PhyloP100		-1.2
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: rs117031141; hg19: chr16-2374394;