21-42271120-T-C

Variant names:

• chr21-42271120-T-C
• rs757350026
• NM_016818.3:c.337T>C
• ABCG1 p.Leu113Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016818.3(ABCG1):​c.337T>C​(p.Leu113Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000021 in 1,431,392 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. L113L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ABCG1 NM_016818.3 synonymous
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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>C	p.Leu113Leu	synonymous	Exon 3 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.337T>C	p.Leu113Leu	synonymous	Exon 3 of 15	NP_004906.3
	ABCG1	NM_207174.1		c.370T>C	p.Leu124Leu	synonymous	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>C	p.Leu113Leu	synonymous	Exon 3 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000398437.1	TSL:1	c.775T>C	p.Leu259Leu	synonymous	Exon 4 of 16	ENSP00000381464.1	E9PGV9
	ABCG1	ENST00000361802.7	TSL:1	c.337T>C	p.Leu113Leu	synonymous	Exon 3 of 15	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431392 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 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: 0.00 AC: 0 AN: 81418

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1099414

Other (OTH) AF: 0.00 AC: 0 AN: 59116

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.2
DANN	Benign	0.77
PhyloP100		4.8

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;