rs757350026

Variant names:

• chr21-42271120-T-A
• rs757350026
• NM_016818.3:c.337T>A
• ABCG1 p.Leu113Met

Your query was ambiguous. Multiple possible variants found:

• chr21-42271120-T-A
• chr21-42271120-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016818.3(ABCG1):​c.337T>A​(p.Leu113Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000978 in 1,431,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L113L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: ABCG1 NM_016818.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78
• Publications: 0 publications found

Genes affected

ABCG1 (HGNC:73): (ATP binding cassette subfamily G member 1) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.337T>A	p.Leu113Met	missense	Exon 3 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.337T>A	p.Leu113Met	missense	Exon 3 of 15	NP_004906.3
	ABCG1	NM_207174.1		c.370T>A	p.Leu124Met	missense	Exon 3 of 15	NP_997057.1	P45844-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.337T>A	p.Leu113Met	missense	Exon 3 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000398437.1	TSL:1	c.775T>A	p.Leu259Met	missense	Exon 4 of 16	ENSP00000381464.1	E9PGV9
	ABCG1	ENST00000361802.7	TSL:1	c.337T>A	p.Leu113Met	missense	Exon 3 of 15	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000889 AC: 2 AN: 225076 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000383

GnomAD4 exome AF: 0.00000978 AC: 14 AN: 1431392 Hom.: 0 Cov.: 30 AF XY: 0.00000843 AC XY: 6 AN XY: 711632

African (AFR) AF: 0.00 AC: 0 AN: 31794

American (AMR) AF: 0.00 AC: 0 AN: 38818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25476

East Asian (EAS) AF: 0.00 AC: 0 AN: 36576

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5704

European-Non Finnish (NFE) AF: 0.0000100 AC: 11 AN: 1099414

Other (OTH) AF: 0.0000169 AC: 1 AN: 59116

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	0.60	N
PhyloP100		4.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.27
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.014	D
Varity_R		0.31
gMVP		0.54
Mutation Taster		=26/74	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs757350026;

hg19: chr21-43691230;