NM_001089.3:c.991-105C>A

Variant names:

• chr16-2317508-G-T
• rs323066
• NM_001089.3:c.991-105C>A

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.991-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,584,850 control chromosomes in the GnomAD database, including 19,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1609 hom., cov: 31)
  • Exomes 𝑓: 0.15 (18135 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.174
• Publications: 15 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=-0.87).
• BP6: Variant 16-2317508-G-T is Benign according to our data. Variant chr16-2317508-G-T is described in ClinVar as Benign. ClinVar VariationId is 1239487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 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.991-105C>A		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.991-105C>A		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.991-105C>A		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000563623.5	TSL:1	n.1554-105C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21345 AN: 151408 Hom.: 1611 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.153 AC: 219664 AN: 1433324 Hom.: 18135 Cov.: 29 AF XY: 0.151 AC XY: 107765 AN XY: 713532

African (AFR) AF: 0.127 AC: 4188 AN: 32884

American (AMR) AF: 0.0761 AC: 3389 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4322 AN: 25884

East Asian (EAS) AF: 0.0350 AC: 1379 AN: 39448

South Asian (SAS) AF: 0.0731 AC: 6226 AN: 85150

European-Finnish (FIN) AF: 0.164 AC: 8127 AN: 49628

Middle Eastern (MID) AF: 0.182 AC: 1034 AN: 5686

European-Non Finnish (NFE) AF: 0.167 AC: 182226 AN: 1090724

Other (OTH) AF: 0.148 AC: 8773 AN: 59394

GnomAD4 genome AF: 0.141 AC: 21345 AN: 151526 Hom.: 1609 Cov.: 31 AF XY: 0.139 AC XY: 10293 AN XY: 74038

African (AFR) AF: 0.125 AC: 5154 AN: 41292

American (AMR) AF: 0.122 AC: 1850 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.0332 AC: 170 AN: 5122

South Asian (SAS) AF: 0.0668 AC: 320 AN: 4790

European-Finnish (FIN) AF: 0.166 AC: 1742 AN: 10514

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11051 AN: 67838

Other (OTH) AF: 0.142 AC: 298 AN: 2100

Alfa AF: 0.155 Hom.: 3239

Bravo AF: 0.141

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.31
PhyloP100		0.17
Mutation Taster		=99/1	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: rs323066; hg19: chr16-2367509; COSMIC: COSV57062441;