Variant 9-137011907-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001606.5(ABCA2):c.5472C>T(p.His1824His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,611,604 control chromosomes in the GnomAD database, including 379,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34188 hom., cov: 33)

Exomes 𝑓: 0.69 ( 345043 hom. )

Consequence

ABCA2
NM_001606.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.82

Variant links:

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]

ABCA2 links:

ABCA2 (HGNC:):

ABCA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 9-137011907-G-A is Benign according to our data. Variant chr9-137011907-G-A is described in ClinVar as [Benign]. Clinvar id is 1098723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA2	NM_001606.5 linkuse as main transcript	c.5472C>T	p.His1824His	synonymous_variant	35/49	ENST00000341511.11	NP_001597.2	Q9BZC7-3
ABCA2	NM_212533.3 linkuse as main transcript	c.5562C>T	p.His1854His	synonymous_variant	35/49		NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1 linkuse as main transcript	c.5469C>T	p.His1823His	synonymous_variant	34/48		NP_001397971.1
ABCA2	XM_047422921.1 linkuse as main transcript	c.5559C>T	p.His1853His	synonymous_variant	34/48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11 linkuse as main transcript	c.5472C>T	p.His1824His	synonymous_variant	35/49	5	NM_001606.5	ENSP00000344155.6		Q9BZC7-3

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101680

AN:

151994

Hom.:

34170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.709

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.678

GnomAD3 exomes

AF:

0.674

AC:

165665

AN:

245744

Hom.:

56590

AF XY:

0.684

AC XY:

91632

AN XY:

133904

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.709

Gnomad EAS exome

AF:

0.809

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.655

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.686

AC:

1001341

AN:

1459492

Hom.:

345043

Cov.:

AF XY:

0.688

AC XY:

499289

AN XY:

725998

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.532

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.812

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.661

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.691

GnomAD4 genome

AF:

0.669

AC:

101736

AN:

152112

Hom.:

34188

Cov.:

AF XY:

0.668

AC XY:

49680

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.613

Gnomad4 ASJ

AF:

0.709

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.749

Gnomad4 FIN

AF:

0.643

Gnomad4 NFE

AF:

0.689

Gnomad4 OTH

AF:

0.681

Alfa

AF:

0.693

Hom.:

42492

Bravo

AF:

0.664

Asia WGS

AF:

0.753

AC:

2617

AN:

3478

EpiCase

AF:

0.701

EpiControl

AF:

0.704

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

May 18, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.4

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over