9-137008334-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001606.5(ABCA2):c.7275+82C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 1,490,822 control chromosomes in the GnomAD database, including 684,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (65950 hom., cov: 33)
  • Exomes 𝑓: 0.96 (618410 hom.)
• Consequence: ABCA2 NM_001606.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.02

Genes affected

ABCA2 (HGNC:32): (ATP binding cassette subfamily A member 2) 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. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 9-137008334-G-C is Benign according to our data. Variant chr9-137008334-G-C is described in ClinVar as [Benign]. Clinvar id is 1185354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA2	NM_001606.5	c.7275+82C>G		intron_variant		ENST00000341511.11
ABCA2	NM_001411042.1	c.7272+82C>G		intron_variant
ABCA2	NM_212533.3	c.7365+82C>G		intron_variant
ABCA2	XM_047422921.1	c.7362+82C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA2	ENST00000341511.11	c.7275+82C>G		intron_variant		5	NM_001606.5	P3

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141303 AN: 152104 Hom.: 65917 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.944

GnomAD3 exomes AF: 0.964 AC: 133193 AN: 138170 Hom.: 64285 AF XY: 0.966 AC XY: 72442 AN XY: 75000

Gnomad AFR exome AF: 0.829

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.963

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.973

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.964

Gnomad OTH exome AF: 0.966

GnomAD4 exome AF: 0.961 AC: 1286292 AN: 1338600 Hom.: 618410 Cov.: 23 AF XY: 0.962 AC XY: 637735 AN XY: 663268

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.975

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.975

Gnomad4 FIN exome AF: 0.971

Gnomad4 NFE exome AF: 0.962

Gnomad4 OTH exome AF: 0.958

GnomAD4 genome AF: 0.929 AC: 141394 AN: 152222 Hom.: 65950 Cov.: 33 AF XY: 0.933 AC XY: 69430 AN XY: 74418

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.945

Alfa AF: 0.954 Hom.: 7385

Bravo AF: 0.925

Asia WGS AF: 0.975 AC: 3392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual developmental disorder with poor growth and with or without seizures or ataxia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.066
Dann	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4880186; hg19: chr9-139902786; COSMIC: COSV55797095; COSMIC: COSV55797095;