9-137007762-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.*167T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 941,384 control chromosomes in the GnomAD database, including 431,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (65662 hom., cov: 35)
  • Exomes 𝑓: 0.96 (365811 hom.)
• Consequence: ABCA2 NM_001606.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

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=-0.89).
• BP6: Variant 9-137007762-A-G is Benign according to our data. Variant chr9-137007762-A-G is described in ClinVar as [Benign]. Clinvar id is 1185555.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.*167T>C		3_prime_UTR_variant	49/49	ENST00000341511.11
ABCA2	NM_001411042.1	c.*167T>C		3_prime_UTR_variant	48/48
ABCA2	NM_212533.3	c.*167T>C		3_prime_UTR_variant	49/49
ABCA2	XM_047422921.1	c.*167T>C		3_prime_UTR_variant	48/48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA2	ENST00000341511.11	c.*167T>C		3_prime_UTR_variant	49/49	5	NM_001606.5	P3

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141040 AN: 152198 Hom.: 65633 Cov.: 35

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.932

GnomAD4 exome AF: 0.963 AC: 759521 AN: 789068 Hom.: 365811 Cov.: 10 AF XY: 0.964 AC XY: 390746 AN XY: 405484

Gnomad4 AFR exome AF: 0.826

Gnomad4 AMR exome AF: 0.973

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: 0.962

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.926 AC: 141119 AN: 152316 Hom.: 65662 Cov.: 35 AF XY: 0.929 AC XY: 69218 AN XY: 74480

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.933

Alfa AF: 0.951 Hom.: 5878

Bravo AF: 0.921

Asia WGS AF: 0.982 AC: 3413 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	-0.89
Cadd	Benign	0.20
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10870161; hg19: chr9-139902214;