rs547612173

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-137028867-C-G
• chr9-137028867-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_212533.3(ABCA2):​c.6G>C​(p.Gly2Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000034 in 1,174,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G2G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ABCA2 NM_212533.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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>C	p.Gly2Gly	synonymous_variant	Exon 1 of 49		NP_997698.1
ABCA2	XM_047422921.1	c.6G>C	p.Gly2Gly	synonymous_variant	Exon 1 of 48		XP_047278877.1
LINC02908	NR_171031.1	n.448+956C>G		intron_variant	Intron 1 of 2

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000340 AC: 4 AN: 1174994 Hom.: 0 Cov.: 33 AF XY: 0.00000516 AC XY: 3 AN XY: 581710

African (AFR) AF: 0.00 AC: 0 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: 0.0000129 AC: 1 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: 0.00000320 AC: 3 AN: 937470

Other (OTH) AF: 0.00 AC: 0 AN: 42410

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		-1.4
PromoterAI		0.026	Neutral

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;