rs117031141

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-2324393-G-A
• chr16-2324393-G-C
• chr16-2324393-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 162675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2324393-G-A is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.447+11C>T		intron_variant	Intron 6 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.447+11C>T		intron_variant	Intron 6 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.447+11C>T		intron_variant	Intron 6 of 31	1		ENSP00000371818.3
ABCA3	ENST00000567910.1	c.447+11C>T		intron_variant	Intron 5 of 5	1		ENSP00000454397.1
ABCA3	ENST00000563623.5	n.1010+11C>T		intron_variant	Intron 6 of 19	1

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

GnomAD3 exomes AF: 0.0179 AC: 3797 AN: 211748 Hom.: 47 AF XY: 0.0185 AC XY: 2133 AN XY: 115476

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 SAS exome AF: 0.0113

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

Gnomad4 AFR exome AF: 0.00362

Gnomad4 AMR exome AF: 0.00829

Gnomad4 ASJ exome AF: 0.0269

Gnomad4 EAS exome AF: 0.0000770

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0266

Gnomad4 OTH exome AF: 0.0211

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

Gnomad4 AFR AF: 0.00462

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0252 Hom.: 6

Bravo AF: 0.0168

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

447+11C>T in intron 6 of ABCA3: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 2.4% (210/8594) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs117031141). -

Interstitial lung disease due to ABCA3 deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary pulmonary alveolar proteinosis Benign:1

Aug 23, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs117031141; hg19: chr16-2374394;