21-42232943-C-T

Variant names:

• chr21-42232943-C-T
• rs225440
• NM_016818.3:c.286+7029C>T

Variant summary

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

The NM_016818.3(ABCG1):​c.286+7029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,154 control chromosomes in the GnomAD database, including 15,464 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 0.44 (15464 hom., cov: 33)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 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.286+7029C>T		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.286+7029C>T		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.319+7029C>T		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.286+7029C>T		intron	N/A	ENSP00000381467.3
	ABCG1	ENST00000361802.7	TSL:1	c.286+7029C>T		intron	N/A	ENSP00000354995.2
	ABCG1	ENST00000343687.7	TSL:1	c.319+7029C>T		intron	N/A	ENSP00000339744.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67250 AN: 152036 Hom.: 15442 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.442 AC: 67315 AN: 152154 Hom.: 15464 Cov.: 33 AF XY: 0.436 AC XY: 32445 AN XY: 74390

African (AFR) AF: 0.565 AC: 23433 AN: 41494

American (AMR) AF: 0.427 AC: 6538 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1543 AN: 5182

South Asian (SAS) AF: 0.372 AC: 1795 AN: 4824

European-Finnish (FIN) AF: 0.311 AC: 3296 AN: 10584

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27373 AN: 67988

Other (OTH) AF: 0.464 AC: 980 AN: 2112

Alfa AF: 0.421 Hom.: 39897

Bravo AF: 0.456

Asia WGS AF: 0.335 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		0.27
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: rs225440; hg19: chr21-43653053;