chr21-42219222-CCCG-C

Variant names:

• chr21-42219222-CCCG-C
• rs2234716
• NM_016818.3:c.-11_-9delGCC

Variant summary

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

The NM_016818.3(ABCG1):​c.-11_-9delGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,371,458 control chromosomes in the GnomAD database, including 483 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.035 (284 hom., cov: 26)
  • Exomes 𝑓: 0.010 (199 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-CCCG-C is Benign according to our data. Variant chr21-42219222-CCCG-C is described in ClinVar as Benign. ClinVar VariationId is 3059271.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.-11_-9delGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-11_-9delGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6419_49-6417delGCC		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.-11_-9delGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-11_-9delGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6419_49-6417delGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5158 AN: 150108 Hom.: 281 Cov.: 26

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00356

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.000847

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0350 AC: 2669 AN: 76150 AF XY: 0.0309

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.0883

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.0264

Gnomad FIN exome AF: 0.00847

Gnomad NFE exome AF: 0.0177

Gnomad OTH exome AF: 0.0306

GnomAD4 exome AF: 0.0101 AC: 12283 AN: 1221246 Hom.: 199 AF XY: 0.00947 AC XY: 5688 AN XY: 600720

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

African (AFR) AF: 0.129 AC: 3284 AN: 25364

American (AMR) AF: 0.0676 AC: 1885 AN: 27878

Ashkenazi Jewish (ASJ) AF: 0.00756 AC: 158 AN: 20912

East Asian (EAS) AF: 0.00855 AC: 241 AN: 28194

South Asian (SAS) AF: 0.00950 AC: 619 AN: 65162

European-Finnish (FIN) AF: 0.00623 AC: 194 AN: 31134

Middle Eastern (MID) AF: 0.00947 AC: 47 AN: 4964

European-Non Finnish (NFE) AF: 0.00520 AC: 5028 AN: 967216

Other (OTH) AF: 0.0164 AC: 827 AN: 50422

⚠️ 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: 0.0346 AC: 5194 AN: 150212 Hom.: 284 Cov.: 26 AF XY: 0.0339 AC XY: 2488 AN XY: 73362

African (AFR) AF: 0.107 AC: 4370 AN: 41032

American (AMR) AF: 0.0453 AC: 684 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3448

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5080

South Asian (SAS) AF: 0.00315 AC: 15 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10180

Middle Eastern (MID) AF: 0.0310 AC: 9 AN: 290

European-Non Finnish (NFE) AF: 0.000847 AC: 57 AN: 67322

Other (OTH) AF: 0.0275 AC: 57 AN: 2076

Alfa AF: 0.0218 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		=297/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2234716; hg19: chr21-43639332; COSMIC: COSV59202536; COSMIC: COSV59202536;