ENST00000464157.1:n.347C>G

Variant names:

• chr9-137008334-G-C
• rs4880186
• ENST00000464157.1:n.347C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000464157.1(ABCA2):​n.347C>G variant causes a non coding transcript exon 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 ENST00000464157.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.02
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with poor growth and with or without seizures or ataxia

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ABCA2	NM_001606.5	c.7275+82C>G		intron_variant	Intron 48 of 48	ENST00000341511.11	NP_001597.2
ABCA2	NM_212533.3	c.7365+82C>G		intron_variant	Intron 48 of 48		NP_997698.1
ABCA2	NM_001411042.1	c.7272+82C>G		intron_variant	Intron 47 of 47		NP_001397971.1
ABCA2	XM_047422921.1	c.7362+82C>G		intron_variant	Intron 47 of 47		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11	c.7275+82C>G		intron_variant	Intron 48 of 48	5	NM_001606.5	ENSP00000344155.6

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

GnomAD2 exomes AF: 0.964 AC: 133193 AN: 138170 AF XY: 0.966

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 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

African (AFR) AF: 0.827 AC: 25149 AN: 30406

American (AMR) AF: 0.975 AC: 34722 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 23917 AN: 24860

East Asian (EAS) AF: 0.999 AC: 35441 AN: 35462

South Asian (SAS) AF: 0.975 AC: 76008 AN: 77932

European-Finnish (FIN) AF: 0.971 AC: 38739 AN: 39894

Middle Eastern (MID) AF: 0.971 AC: 5434 AN: 5598

European-Non Finnish (NFE) AF: 0.962 AC: 993020 AN: 1032594

Other (OTH) AF: 0.958 AC: 53862 AN: 56226

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

African (AFR) AF: 0.832 AC: 34543 AN: 41500

American (AMR) AF: 0.961 AC: 14712 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5165 AN: 5172

South Asian (SAS) AF: 0.978 AC: 4719 AN: 4826

European-Finnish (FIN) AF: 0.966 AC: 10250 AN: 10612

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65495 AN: 68018

Other (OTH) AF: 0.945 AC: 1995 AN: 2112

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.066
DANN	Benign	0.31
PhyloP100		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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