9-137008260-A-G

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+156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 913,584 control chromosomes in the GnomAD database, including 427,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (70799 hom., cov: 32)
  • Exomes 𝑓: 0.97 (356826 hom.)
• Consequence: ABCA2 NM_001606.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.286

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=-0.9).
• BP6: Variant 9-137008260-A-G is Benign according to our data. Variant chr9-137008260-A-G is described in ClinVar as [Benign]. Clinvar id is 1185556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA2	NM_001606.5	c.7275+156T>C		intron_variant		ENST00000341511.11
ABCA2	NM_001411042.1	c.7272+156T>C		intron_variant
ABCA2	NM_212533.3	c.7365+156T>C		intron_variant
ABCA2	XM_047422921.1	c.7362+156T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA2	ENST00000341511.11	c.7275+156T>C		intron_variant		5	NM_001606.5	P3

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146730 AN: 152162 Hom.: 70749 Cov.: 32

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.961

GnomAD3 exomes AF: 0.974 AC: 127432 AN: 130874 Hom.: 62053 AF XY: 0.974 AC XY: 69658 AN XY: 71534

Gnomad AFR exome AF: 0.955

Gnomad AMR exome AF: 0.983

Gnomad ASJ exome AF: 0.963

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.983

Gnomad FIN exome AF: 0.969

Gnomad NFE exome AF: 0.964

Gnomad OTH exome AF: 0.973

GnomAD4 exome AF: 0.968 AC: 737033 AN: 761304 Hom.: 356826 Cov.: 10 AF XY: 0.968 AC XY: 385436 AN XY: 398034

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.984

Gnomad4 FIN exome AF: 0.971

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 0.966

GnomAD4 genome AF: 0.964 AC: 146838 AN: 152280 Hom.: 70799 Cov.: 32 AF XY: 0.966 AC XY: 71891 AN XY: 74442

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.986

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.962

Alfa AF: 0.963 Hom.: 16283

Bravo AF: 0.964

Asia WGS AF: 0.991 AC: 3447 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.9
Dann	Benign	0.66

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: rs4880185; hg19: chr9-139902712; COSMIC: COSV55803117; COSMIC: COSV55803117;