rs78286222

Positions:

• chr16-2326475-T-C
• chr16-2326475-T-G

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.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,608,992 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (23 hom.)
• Consequence: ABCA3 NM_001089.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.11

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-2326475-T-C is Benign according to our data. Variant chr16-2326475-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 226453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00973 (1482/152332) while in subpopulation AFR AF= 0.0337 (1402/41564). AF 95% confidence interval is 0.0323. There are 23 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.-9A>G		5_prime_UTR_variant	4/33	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.-9A>G		5_prime_UTR_variant	4/33	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.-9A>G		5_prime_UTR_variant	4/32	1		ENSP00000371818.3
ABCA3	ENST00000567910.1	c.-9A>G		5_prime_UTR_variant	3/6	1		ENSP00000454397.1
ABCA3	ENST00000563623.5	n.555A>G		non_coding_transcript_exon_variant	4/20	1

Frequencies

GnomAD3 genomes AF: 0.00972 AC: 1479 AN: 152214 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00248 AC: 594 AN: 239772 Hom.: 5 AF XY: 0.00177 AC XY: 230 AN XY: 129648

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000681

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.00106 AC: 1549 AN: 1456660 Hom.: 23 Cov.: 35 AF XY: 0.000870 AC XY: 630 AN XY: 724084

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome AF: 0.00973 AC: 1482 AN: 152332 Hom.: 23 Cov.: 32 AF XY: 0.00967 AC XY: 720 AN XY: 74488

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00429 Hom.: 5

Bravo AF: 0.0115

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 04, 2020	- -
Likely 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

-9A>G in exon 4 of ABCA3: This variant is not expected to have clinical signific ance because it has been identified in 3.3% (146/4396) of African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.43

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: rs78286222; hg19: chr16-2376476;