NM_016818.3:c.-14_-9dupGCCGCC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_016818.3(ABCG1):​c.-14_-9dupGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,468,542 control chromosomes in the GnomAD database, including 856 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.038 (154 hom., cov: 26)
  • Exomes 𝑓: 0.041 (702 hom.)
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 21-42219222-C-CCCGCCG is Benign according to our data. Variant chr21-42219222-C-CCCGCCG is described in ClinVar as Benign. ClinVar VariationId is 3037187.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0376 (5652/150262) while in subpopulation NFE AF = 0.0504 (3396/67326). AF 95% confidence interval is 0.049. There are 154 homozygotes in GnomAd4. There are 2622 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 154 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.-14_-9dupGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-14_-9dupGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6422_49-6417dupGCCGCC		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_-9dupGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-14_-9dupGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6422_49-6417dupGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5649 AN: 150158 Hom.: 153 Cov.: 26

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0730

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0365

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0433

GnomAD2 exomes AF: 0.0209 AC: 1595 AN: 76150 AF XY: 0.0224

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0272

GnomAD4 exome AF: 0.0406 AC: 53585 AN: 1318280 Hom.: 702 Cov.: 20 AF XY: 0.0406 AC XY: 26450 AN XY: 651180

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

African (AFR) AF: 0.0196 AC: 531 AN: 27104

American (AMR) AF: 0.0143 AC: 431 AN: 30072

Ashkenazi Jewish (ASJ) AF: 0.0365 AC: 826 AN: 22638

East Asian (EAS) AF: 0.000357 AC: 11 AN: 30784

South Asian (SAS) AF: 0.0295 AC: 2193 AN: 74454

European-Finnish (FIN) AF: 0.0222 AC: 753 AN: 33938

Middle Eastern (MID) AF: 0.0529 AC: 277 AN: 5236

European-Non Finnish (NFE) AF: 0.0447 AC: 46499 AN: 1039490

Other (OTH) AF: 0.0378 AC: 2064 AN: 54564

⚠️ 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: 0.0376 AC: 5652 AN: 150262 Hom.: 154 Cov.: 26 AF XY: 0.0357 AC XY: 2622 AN XY: 73394

African (AFR) AF: 0.0254 AC: 1044 AN: 41060

American (AMR) AF: 0.0356 AC: 538 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.0365 AC: 126 AN: 3448

East Asian (EAS) AF: 0.000591 AC: 3 AN: 5080

South Asian (SAS) AF: 0.0258 AC: 123 AN: 4764

European-Finnish (FIN) AF: 0.0241 AC: 246 AN: 10190

Middle Eastern (MID) AF: 0.0690 AC: 20 AN: 290

European-Non Finnish (NFE) AF: 0.0504 AC: 3396 AN: 67326

Other (OTH) AF: 0.0433 AC: 90 AN: 2078

Alfa AF: 0.0186 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		=299/1	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;