rs150929

Variant names:

• chr16-2278649-G-T
• rs150929
• NM_001089.3:c.4548-191C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2278649-G-T
• chr16-2278649-G-A
• chr16-2278649-G-C

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.4548-191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,118 control chromosomes in the GnomAD database, including 14,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.43 (14248 hom., cov: 33)
• Consequence: ABCA3 NM_001089.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0190
• Publications: 8 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 16-2278649-G-T is Benign according to our data. Variant chr16-2278649-G-T is described in ClinVar as Benign. ClinVar VariationId is 1235998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 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.4548-191C>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.4548-191C>A		intron	N/A	ENSP00000301732.5	Q99758-1
	ABCA3	ENST00000382381.7	TSL:1	c.4374-191C>A		intron	N/A	ENSP00000371818.3	H0Y3H2
	ABCA3	ENST00000967440.1		c.4548-191C>A		intron	N/A	ENSP00000637499.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65397 AN: 152000 Hom.: 14244 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.412

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65425 AN: 152118 Hom.: 14248 Cov.: 33 AF XY: 0.430 AC XY: 31966 AN XY: 74370

African (AFR) AF: 0.478 AC: 19829 AN: 41484

American (AMR) AF: 0.381 AC: 5824 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2665 AN: 5174

South Asian (SAS) AF: 0.514 AC: 2479 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4146 AN: 10578

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27425 AN: 67986

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.401 Hom.: 25298

Bravo AF: 0.427

Asia WGS AF: 0.527 AC: 1832 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	-0.84
CADD	Benign	0.76
DANN	Benign	0.50
PhyloP100		-0.019
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: rs150929; hg19: chr16-2328650;