ENST00000451485.3:n.572+473G>A

Variant names:

• chr3-46370771-C-T
• rs41469351
• ENST00000451485.3:n.572+473G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000451485.3(CCR5AS):​n.572+473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 152,240 control chromosomes in the GnomAD database, including 834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (834 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CCR5AS ENST00000451485.3 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -0.478
• Publications: 21 publications found

Genes affected

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

CCR5 (HGNC:1606): (C-C motif chemokine receptor 5) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-46370771-C-T is Benign according to our data. Variant chr3-46370771-C-T is described in ClinVar as Benign. ClinVar VariationId is 8190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451485.3. 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
	CCR5AS	NR_125406.2	MANE Select	n.572+473G>A		intron	N/A
	CCR5	NM_000579.4		c.-229C>T		5_prime_UTR	Exon 2 of 3	NP_000570.1	Q38L21
	CCR5	NM_001100168.2		c.-65-164C>T		intron	N/A	NP_001093638.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.572+473G>A		intron	N/A
	CCR5AS	ENST00000701879.2		n.462+473G>A		intron	N/A
	CCR5AS	ENST00000717843.1		n.324+473G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8823 AN: 152122 Hom.: 835 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0580 AC: 8831 AN: 152240 Hom.: 834 Cov.: 33 AF XY: 0.0555 AC XY: 4127 AN XY: 74422

African (AFR) AF: 0.204 AC: 8467 AN: 41500

American (AMR) AF: 0.0166 AC: 254 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68022

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0313 Hom.: 114

Bravo AF: 0.0667

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Human immunodeficiency virus type 1, increased perinatal transmission of (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.48
PromoterAI		-0.0016	Neutral
Mutation Taster		=300/0	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs41469351; hg19: chr3-46412262;