21-42219222-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCG

Variant names:

• chr21-42219222-CCCGCCGCCGCCG-C
• rs2234716
• NM_016818.3:c.-20_-9delGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_016818.3(ABCG1):​c.-20_-9delGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,474,122 control chromosomes in the GnomAD database, including 13 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0020 (13 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.20
• 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 21-42219222-CCCGCCGCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCGCCGCCG-C is described in ClinVar as Benign. ClinVar VariationId is 3053710.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

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.-20_-9delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-20_-9delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6428_49-6417delGCCGCCGCCGCC		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.-20_-9delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-20_-9delGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6428_49-6417delGCCGCCGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 257 AN: 150180 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00371

Gnomad ASJ AF: 0.0102

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00180

Gnomad OTH AF: 0.00243

GnomAD2 exomes AF: 0.00457 AC: 348 AN: 76150 AF XY: 0.00403

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.00876

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.000472

Gnomad FIN exome AF: 0.00101

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00584

GnomAD4 exome AF: 0.00204 AC: 2698 AN: 1323838 Hom.: 13 AF XY: 0.00199 AC XY: 1301 AN XY: 653840

African (AFR) AF: 0.000441 AC: 12 AN: 27182

American (AMR) AF: 0.00652 AC: 197 AN: 30230

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 278 AN: 22844

East Asian (EAS) AF: 0.0000325 AC: 1 AN: 30786

South Asian (SAS) AF: 0.000493 AC: 37 AN: 75020

European-Finnish (FIN) AF: 0.00141 AC: 48 AN: 34022

Middle Eastern (MID) AF: 0.000761 AC: 4 AN: 5258

European-Non Finnish (NFE) AF: 0.00194 AC: 2022 AN: 1043732

Other (OTH) AF: 0.00181 AC: 99 AN: 54764

GnomAD4 genome AF: 0.00171 AC: 257 AN: 150284 Hom.: 0 Cov.: 26 AF XY: 0.00174 AC XY: 128 AN XY: 73406

African (AFR) AF: 0.000706 AC: 29 AN: 41070

American (AMR) AF: 0.00370 AC: 56 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 35 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00108 AC: 11 AN: 10190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00180 AC: 121 AN: 67334

Other (OTH) AF: 0.00241 AC: 5 AN: 2078

Alfa AF: 0.00207 Hom.: 167

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		=294/6	polymorphism

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;