NM_016818.3:c.-23_-9delGCCGCCGCCGCCGCC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_016818.3(ABCG1):​c.-23_-9delGCCGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,474,162 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Likely 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 -1 ACMG points.

• BP6: Variant 21-42219222-CCCGCCGCCGCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCGCCGCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3047646.Status of the report is no_assertion_criteria_provided, 0 stars.

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_-9delGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_058198.2
	ABCG1	NM_004915.4		c.-23_-9delGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	NP_004906.3
	ABCG1	NM_207627.2		c.49-6431_49-6417delGCCGCCGCCGCCGCC		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_-9delGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000361802.7	TSL:1	c.-23_-9delGCCGCCGCCGCCGCC		5_prime_UTR	Exon 1 of 15	ENSP00000354995.2	P45844-1
	ABCG1	ENST00000398457.6	TSL:1	c.49-6431_49-6417delGCCGCCGCCGCCGCC		intron	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150180 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000242 AC: 32 AN: 1323878 Hom.: 0 AF XY: 0.0000336 AC XY: 22 AN XY: 653864

African (AFR) AF: 0.00 AC: 0 AN: 27182

American (AMR) AF: 0.0000662 AC: 2 AN: 30230

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

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

South Asian (SAS) AF: 0.000160 AC: 12 AN: 75016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34024

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

European-Non Finnish (NFE) AF: 0.0000163 AC: 17 AN: 1043774

Other (OTH) AF: 0.0000183 AC: 1 AN: 54766

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150284 Hom.: 0 Cov.: 26 AF XY: 0.0000136 AC XY: 1 AN XY: 73406

African (AFR) AF: 0.00 AC: 0 AN: 41070

American (AMR) AF: 0.00 AC: 0 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.000197 AC: 1 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: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 167

ClinVar

ClinVar submissions

Significance: Likely 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

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;