rs313908

Variant names:

• chr16-2288362-C-G
• rs313908
• NM_001089.3:c.2701-33G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-2288362-C-G
• chr16-2288362-C-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.2701-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,534,392 control chromosomes in the GnomAD database, including 423,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38880 hom., cov: 33)
  • Exomes 𝑓: 0.74 (384615 hom.)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.184
• 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=-0.84).
• BP6: Variant 16-2288362-C-G is Benign according to our data. Variant chr16-2288362-C-G is described in ClinVar as Benign. ClinVar VariationId is 1185445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.2701-33G>C		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.2701-33G>C		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.2527-33G>C		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000967440.1		c.2701-33G>C		intron	N/A	ENSP00000637499.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107459 AN: 152034 Hom.: 38852 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.715

GnomAD2 exomes AF: 0.789 AC: 110093 AN: 139536 AF XY: 0.792

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.716

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.743 AC: 1026806 AN: 1382240 Hom.: 384615 Cov.: 45 AF XY: 0.747 AC XY: 509046 AN XY: 681676

African (AFR) AF: 0.560 AC: 17697 AN: 31604

American (AMR) AF: 0.847 AC: 30254 AN: 35728

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 17970 AN: 25118

East Asian (EAS) AF: 0.973 AC: 34802 AN: 35776

South Asian (SAS) AF: 0.874 AC: 69180 AN: 79110

European-Finnish (FIN) AF: 0.784 AC: 27113 AN: 34566

Middle Eastern (MID) AF: 0.708 AC: 3881 AN: 5484

European-Non Finnish (NFE) AF: 0.727 AC: 783133 AN: 1077072

Other (OTH) AF: 0.740 AC: 42776 AN: 57782

GnomAD4 genome AF: 0.707 AC: 107530 AN: 152152 Hom.: 38880 Cov.: 33 AF XY: 0.715 AC XY: 53191 AN XY: 74390

African (AFR) AF: 0.563 AC: 23378 AN: 41498

American (AMR) AF: 0.784 AC: 11989 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2483 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5049 AN: 5172

South Asian (SAS) AF: 0.877 AC: 4232 AN: 4824

European-Finnish (FIN) AF: 0.798 AC: 8452 AN: 10598

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49502 AN: 67978

Other (OTH) AF: 0.718 AC: 1520 AN: 2116

Alfa AF: 0.682 Hom.: 4557

Bravo AF: 0.697

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Interstitial lung disease due to ABCA3 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.38
PhyloP100		-0.18
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: rs313908; hg19: chr16-2338363;