chr16-2317508-G-T

Position:

• chr16-2317508-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000301732.10(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 ENST00000301732.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.174

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.991-105C>A		intron_variant		ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.991-105C>A		intron_variant		1	NM_001089.3	ENSP00000301732	P1
ABCA3	ENST00000382381.7	c.991-105C>A		intron_variant		1		ENSP00000371818
ABCA3	ENST00000563623.5	n.1554-105C>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0761

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.0731

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.148

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0332

Gnomad4 SAS AF: 0.0668

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.142

Alfa AF: 0.155 Hom.: 2584

Bravo AF: 0.141

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.31

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: rs323066; hg19: chr16-2367509; COSMIC: COSV57062441;