ENST00000459850.5:n.7688T>C

Variant names:

• chr9-137007762-A-G
• rs10870161
• ENST00000459850.5:n.7688T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000459850.5(ABCA2):​n.7688T>C 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 0.957 in 941,384 control chromosomes in the GnomAD database, including 431,473 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.93 (65662 hom., cov: 35)
  • Exomes 𝑓: 0.96 (365811 hom.)
• Consequence: ABCA2 ENST00000459850.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.62
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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 rank	MANE	Protein	UniProt
ABCA2	NM_001606.5	c.*167T>C		3_prime_UTR_variant	Exon 49 of 49	ENST00000341511.11	NP_001597.2
ABCA2	NM_212533.3	c.*167T>C		3_prime_UTR_variant	Exon 49 of 49		NP_997698.1
ABCA2	NM_001411042.1	c.*167T>C		3_prime_UTR_variant	Exon 48 of 48		NP_001397971.1
ABCA2	XM_047422921.1	c.*167T>C		3_prime_UTR_variant	Exon 48 of 48		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11	c.*167T>C		3_prime_UTR_variant	Exon 49 of 49	5	NM_001606.5	ENSP00000344155.6

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

African (AFR) AF: 0.826 AC: 16230 AN: 19648

American (AMR) AF: 0.973 AC: 29565 AN: 30380

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 18118 AN: 18836

East Asian (EAS) AF: 1.00 AC: 32712 AN: 32714

South Asian (SAS) AF: 0.984 AC: 60804 AN: 61788

European-Finnish (FIN) AF: 0.971 AC: 31208 AN: 32150

Middle Eastern (MID) AF: 0.964 AC: 2655 AN: 2754

European-Non Finnish (NFE) AF: 0.962 AC: 532258 AN: 553218

Other (OTH) AF: 0.957 AC: 35971 AN: 37580

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

African (AFR) AF: 0.826 AC: 34332 AN: 41552

American (AMR) AF: 0.956 AC: 14625 AN: 15306

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

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.985 AC: 4761 AN: 4832

European-Finnish (FIN) AF: 0.966 AC: 10258 AN: 10624

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65475 AN: 68026

Other (OTH) AF: 0.933 AC: 1972 AN: 2114

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: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	-0.89
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-2.6
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)		0.030		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: rs10870161; hg19: chr9-139902214;