9-137028867-C-T

Variant names:

• chr9-137028867-C-T
• rs547612173
• ENST00000459850.5:n.49G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_212533.3(ABCA2):​c.6G>A​(p.Gly2Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,327,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: ABCA2 NM_212533.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-137028867-C-T is Benign according to our data. Variant chr9-137028867-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.41 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA2	NM_212533.3	c.6G>A	p.Gly2Gly	synonymous_variant	Exon 1 of 49		NP_997698.1
ABCA2	XM_047422921.1	c.6G>A	p.Gly2Gly	synonymous_variant	Exon 1 of 48		XP_047278877.1
LINC02908	NR_171031.1	n.448+956C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000459850.5	n.49G>A		non_coding_transcript_exon_variant	Exon 1 of 47	1
ABCA2	ENST00000487109.5	n.6G>A		non_coding_transcript_exon_variant	Exon 1 of 47	1		ENSP00000418662.1
ABCA2	ENST00000614293.5	c.6G>A	p.Gly2Gly	synonymous_variant	Exon 1 of 49	5		ENSP00000481105.2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00000969 AC: 2 AN: 206462 AF XY: 0.00000870

Gnomad AFR exome AF: 0.0000886

Gnomad AMR exome AF: 0.0000364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000851 AC: 10 AN: 1174994 Hom.: 0 Cov.: 33 AF XY: 0.00000344 AC XY: 2 AN XY: 581710

African (AFR) AF: 0.000391 AC: 9 AN: 23016

American (AMR) AF: 0.00 AC: 0 AN: 31012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15960

East Asian (EAS) AF: 0.00 AC: 0 AN: 12100

South Asian (SAS) AF: 0.00 AC: 0 AN: 77646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 937470

Other (OTH) AF: 0.0000236 AC: 1 AN: 42410

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74476

African (AFR) AF: 0.000385 AC: 16 AN: 41576

American (AMR) AF: 0.0000653 AC: 1 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000101 Hom.: 0

Bravo AF: 0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ABCA2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.85
PhyloP100		-1.4
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs547612173; hg19: chr9-139923319;