21-42219222-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCG

Variant names:

• chr21-42219222-CCCGCCG-C
• rs2234716
• NM_016818.3:c.-14_-9delGCCGCC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_016818.3(ABCG1):​c.-14_-9delGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,472,354 control chromosomes in the GnomAD database, including 12,832 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1595 hom., cov: 26)
  • Exomes 𝑓: 0.14 (11237 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.18
• 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]

LOC105372814 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 21-42219222-CCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCG-C is described in ClinVar as Benign. ClinVar VariationId is 3059244.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.-14_-9delGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-14_-9delGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6422_49-6417delGCCGCC		intron	N/A	NP_997510.1	P45844-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.-14_-9delGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-14_-9delGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6422_49-6417delGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20669 AN: 150124 Hom.: 1596 Cov.: 26

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.233 AC: 17772 AN: 76150 AF XY: 0.229

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.139 AC: 183928 AN: 1322126 Hom.: 11237 AF XY: 0.141 AC XY: 91765 AN XY: 653006

African (AFR) AF: 0.0816 AC: 2209 AN: 27076

American (AMR) AF: 0.191 AC: 5755 AN: 30160

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4290 AN: 22786

East Asian (EAS) AF: 0.210 AC: 6451 AN: 30730

South Asian (SAS) AF: 0.162 AC: 12113 AN: 74878

European-Finnish (FIN) AF: 0.248 AC: 8410 AN: 33950

Middle Eastern (MID) AF: 0.194 AC: 1020 AN: 5252

European-Non Finnish (NFE) AF: 0.130 AC: 135373 AN: 1042614

Other (OTH) AF: 0.152 AC: 8307 AN: 54680

GnomAD4 genome AF: 0.138 AC: 20664 AN: 150228 Hom.: 1595 Cov.: 26 AF XY: 0.143 AC XY: 10461 AN XY: 73368

African (AFR) AF: 0.0776 AC: 3187 AN: 41056

American (AMR) AF: 0.159 AC: 2411 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 638 AN: 3446

East Asian (EAS) AF: 0.235 AC: 1196 AN: 5080

South Asian (SAS) AF: 0.156 AC: 740 AN: 4758

European-Finnish (FIN) AF: 0.266 AC: 2704 AN: 10178

Middle Eastern (MID) AF: 0.166 AC: 48 AN: 290

European-Non Finnish (NFE) AF: 0.138 AC: 9282 AN: 67320

Other (OTH) AF: 0.130 AC: 271 AN: 2078

Alfa AF: 0.0889 Hom.: 167

Bravo AF: 0.135

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ABCG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=296/4	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2234716; hg19: chr21-43639332;