21-42264346-G-A

Variant names:

• chr21-42264346-G-A
• rs225388
• NM_016818.3:c.287-6724G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016818.3(ABCG1):​c.287-6724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,086 control chromosomes in the GnomAD database, including 14,879 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14879 hom., cov: 33)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.287-6724G>A		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.287-6724G>A		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.320-6724G>A		intron	N/A	NP_997057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.287-6724G>A		intron	N/A	ENSP00000381467.3
	ABCG1	ENST00000398437.1	TSL:1	c.724+4207G>A		intron	N/A	ENSP00000381464.1
	ABCG1	ENST00000361802.7	TSL:1	c.287-6724G>A		intron	N/A	ENSP00000354995.2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66102 AN: 151968 Hom.: 14870 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66132 AN: 152086 Hom.: 14879 Cov.: 33 AF XY: 0.427 AC XY: 31736 AN XY: 74358

African (AFR) AF: 0.325 AC: 13466 AN: 41458

American (AMR) AF: 0.477 AC: 7296 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1722 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1929 AN: 5188

South Asian (SAS) AF: 0.387 AC: 1864 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4237 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34034 AN: 67976

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.452 Hom.: 1924

Bravo AF: 0.435

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.61
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs225388; hg19: chr21-43684456;