9-137028813-A-G

Variant names:

• chr9-137028813-A-G
• rs4880189
• ENST00000459850.5:n.103T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_212533.3(ABCA2):​c.60T>C​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,295,756 control chromosomes in the GnomAD database, including 344,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43767 hom., cov: 34)
  • Exomes 𝑓: 0.72 (300824 hom.)
• Consequence: ABCA2 NM_212533.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.402
• Publications: 14 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]

LINC02908 (HGNC:31426): (long intergenic non-protein coding RNA 2908)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-137028813-A-G is Benign according to our data. Variant chr9-137028813-A-G is described in ClinVar as [Benign]. Clinvar id is 1249256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.402 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_212533.3	c.60T>C	p.Ala20Ala	synonymous_variant	Exon 1 of 49		NP_997698.1
ABCA2	XM_047422921.1	c.60T>C	p.Ala20Ala	synonymous_variant	Exon 1 of 48		XP_047278877.1
LINC02908	NR_171031.1	n.448+902A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000459850.5	n.103T>C		non_coding_transcript_exon_variant	Exon 1 of 47	1
ABCA2	ENST00000487109.5	n.60T>C		non_coding_transcript_exon_variant	Exon 1 of 47	1		ENSP00000418662.1
ABCA2	ENST00000614293.5	c.60T>C	p.Ala20Ala	synonymous_variant	Exon 1 of 49	5		ENSP00000481105.2

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115179 AN: 152064 Hom.: 43723 Cov.: 34

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.741 AC: 129830 AN: 175114 AF XY: 0.741

Gnomad AFR exome AF: 0.845

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.753

Gnomad EAS exome AF: 0.770

Gnomad FIN exome AF: 0.700

Gnomad NFE exome AF: 0.731

Gnomad OTH exome AF: 0.750

GnomAD4 exome AF: 0.725 AC: 828870 AN: 1143574 Hom.: 300824 Cov.: 57 AF XY: 0.725 AC XY: 410145 AN XY: 565864

African (AFR) AF: 0.848 AC: 17700 AN: 20884

American (AMR) AF: 0.726 AC: 14503 AN: 19974

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 10788 AN: 14302

East Asian (EAS) AF: 0.768 AC: 8684 AN: 11310

South Asian (SAS) AF: 0.758 AC: 54812 AN: 72358

European-Finnish (FIN) AF: 0.701 AC: 21500 AN: 30674

Middle Eastern (MID) AF: 0.687 AC: 2932 AN: 4270

European-Non Finnish (NFE) AF: 0.719 AC: 668029 AN: 928748

Other (OTH) AF: 0.729 AC: 29922 AN: 41054

GnomAD4 genome AF: 0.758 AC: 115284 AN: 152182 Hom.: 43767 Cov.: 34 AF XY: 0.755 AC XY: 56192 AN XY: 74414

African (AFR) AF: 0.838 AC: 34803 AN: 41550

American (AMR) AF: 0.747 AC: 11422 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2629 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3832 AN: 5148

South Asian (SAS) AF: 0.756 AC: 3654 AN: 4832

European-Finnish (FIN) AF: 0.686 AC: 7262 AN: 10590

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49252 AN: 67974

Other (OTH) AF: 0.750 AC: 1585 AN: 2114

Alfa AF: 0.735 Hom.: 13580

Bravo AF: 0.768

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.50
PhyloP100		0.40
PromoterAI		0.17	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4880189; hg19: chr9-139923265; COSMIC: COSV108104438; COSMIC: COSV108104438;