chr21-42219222-C-CCCGCCGCCGCCGCCGCCG

Variant names:

• chr21-42219222-C-CCCGCCGCCGCCGCCGCCG
• rs2234716
• NM_016818.3:c.-26_-9dupGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016818.3(ABCG1):​c.-26_-9dupGCCGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 150,280 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (4 hom., cov: 26)
  • Exomes 𝑓: 0.000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 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.-26_-9dupGCCGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-26_-9dupGCCGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6434_49-6417dupGCCGCCGCCGCCGCCGCC		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.-26_-9dupGCCGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-26_-9dupGCCGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6434_49-6417dupGCCGCCGCCGCCGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 383 AN: 150176 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.00913

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000397

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000974

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000816 AC: 108 AN: 1323804 Hom.: 0 Cov.: 20 AF XY: 0.0000826 AC XY: 54 AN XY: 653828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00358 AC: 97 AN: 27110

American (AMR) AF: 0.0000331 AC: 1 AN: 30236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22844

East Asian (EAS) AF: 0.00 AC: 0 AN: 30786

South Asian (SAS) AF: 0.00 AC: 0 AN: 75024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1043776

Other (OTH) AF: 0.000146 AC: 8 AN: 54744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00256 AC: 384 AN: 150280 Hom.: 4 Cov.: 26 AF XY: 0.00238 AC XY: 175 AN XY: 73402

African (AFR) AF: 0.00913 AC: 375 AN: 41066

American (AMR) AF: 0.000397 AC: 6 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 10190

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

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67334

Other (OTH) AF: 0.000962 AC: 2 AN: 2078

Alfa AF: 0.00 Hom.: 167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.027
Mutation Taster		=300/0	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;