chr16-2323686-C-T

Position:

chr16-2323686-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000301732.10(ABCA3):c.450G>A(p.Val150=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,614,074 control chromosomes in the GnomAD database, including 575 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 302 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 273 hom. )

Consequence

ABCA3
ENST00000301732.10 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0740

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 16-2323686-C-T is Benign according to our data. Variant chr16-2323686-C-T is described in ClinVar as [Benign]. Clinvar id is 178701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.074 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3 linkuse as main transcript	c.450G>A	p.Val150=	splice_region_variant, synonymous_variant	7/33	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10 linkuse as main transcript	c.450G>A	p.Val150=	splice_region_variant, synonymous_variant	7/33	1	NM_001089.3	ENSP00000301732	P1	Q99758-1
ABCA3	ENST00000382381.7 linkuse as main transcript	c.450G>A	p.Val150=	splice_region_variant, synonymous_variant	7/32	1		ENSP00000371818
ABCA3	ENST00000567910.1 linkuse as main transcript	c.450G>A	p.Val150=	splice_region_variant, synonymous_variant	6/6	1		ENSP00000454397		Q99758-2
ABCA3	ENST00000563623.5 linkuse as main transcript	n.1013G>A		splice_region_variant, non_coding_transcript_exon_variant	7/20	1

Frequencies

GnomAD3 genomes

AF:

0.0340

AC:

5166

AN:

152138

Hom.:

301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.00892

AC:

2244

AN:

251476

Hom.:

109

AF XY:

0.00636

AC XY:

865

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00368

AC:

5377

AN:

1461818

Hom.:

273

Cov.:

AF XY:

0.00312

AC XY:

2268

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.00808

GnomAD4 genome

AF:

0.0340

AC:

5179

AN:

152256

Hom.:

302

Cov.:

AF XY:

0.0331

AC XY:

2465

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0400

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 31, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Val150Val in exon 7 of ABCA3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 11.3% (498/4396) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs74002800). -

Interstitial lung disease due to ABCA3 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2016

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

-0.36

CADD

Benign

8.0

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over