chr21-42219222-C-CCCGCCGCCGCCGCCG

Variant names:

• chr21-42219222-C-CCCGCCGCCGCCGCCG
• rs2234716
• NM_016818.3:c.-23_-9dupGCCGCCGCCGCCGCC

Variant summary

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

The NM_016818.3(ABCG1):​c.-23_-9dupGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 150,282 control chromosomes in the GnomAD database, including 3 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. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 26)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 -5 ACMG points.

• BP6: Variant 21-42219222-C-CCCGCCGCCGCCGCCG is Benign according to our data. Variant chr21-42219222-C-CCCGCCGCCGCCGCCG is described in ClinVar as Benign. ClinVar VariationId is 3053330.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 3 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.-23_-9dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-23_-9dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6431_49-6417dupGCCGCCGCCGCCGCC		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.-23_-9dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-23_-9dupGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6431_49-6417dupGCCGCCGCCGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 447 AN: 150178 Hom.: 3 Cov.: 26

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000530

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.00243

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 165 AN: 1323790 Hom.: 0 Cov.: 20 AF XY: 0.000122 AC XY: 80 AN XY: 653822

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

African (AFR) AF: 0.00447 AC: 121 AN: 27092

American (AMR) AF: 0.0000661 AC: 2 AN: 30236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22842

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

South Asian (SAS) AF: 0.0000267 AC: 2 AN: 75022

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

Middle Eastern (MID) AF: 0.000381 AC: 2 AN: 5256

European-Non Finnish (NFE) AF: 0.0000125 AC: 13 AN: 1043780

Other (OTH) AF: 0.000457 AC: 25 AN: 54750

⚠️ 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: 0.00300 AC: 451 AN: 150282 Hom.: 3 Cov.: 26 AF XY: 0.00290 AC XY: 213 AN XY: 73406

African (AFR) AF: 0.0105 AC: 433 AN: 41068

American (AMR) AF: 0.000529 AC: 8 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 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: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0000446 AC: 3 AN: 67334

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

Alfa AF: 0.00 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		0.027
Mutation Taster		=100/0	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;