3-46372791-G-A

Variant names:

• chr3-46372791-G-A
• rs41352147
• NM_001394783.1:c.-11-101G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394783.1(CCR5):​c.-11-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000641 in 788,944 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 2 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 344 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	NM_001394783.1	MANE Select	c.-11-101G>A		intron	N/A	NP_001381712.1
	CCR5AS	NR_125406.2	MANE Select	n.399-1374C>T		intron	N/A
	CCR5	NM_000579.4		c.-11-101G>A		intron	N/A	NP_000570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	ENST00000292303.5	TSL:1 MANE Select	c.-11-101G>A		intron	N/A	ENSP00000292303.4
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-1374C>T		intron	N/A
	CCR5	ENST00000445772.1	TSL:6	c.-112G>A		5_prime_UTR	Exon 1 of 1	ENSP00000404881.1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152106 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00792

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000254 AC: 162 AN: 636720 Hom.: 1 Cov.: 9 AF XY: 0.000222 AC XY: 73 AN XY: 329442

African (AFR) AF: 0.00771 AC: 130 AN: 16868

American (AMR) AF: 0.000356 AC: 9 AN: 25286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15000

East Asian (EAS) AF: 0.00 AC: 0 AN: 35188

South Asian (SAS) AF: 0.00 AC: 0 AN: 46716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37678

Middle Eastern (MID) AF: 0.000433 AC: 1 AN: 2312

European-Non Finnish (NFE) AF: 0.00000940 AC: 4 AN: 425562

Other (OTH) AF: 0.000561 AC: 18 AN: 32110

GnomAD4 genome AF: 0.00226 AC: 344 AN: 152224 Hom.: 1 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74426

African (AFR) AF: 0.00790 AC: 328 AN: 41536

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.39
PhyloP100		-0.27
PromoterAI		0.00040	Neutral

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: rs41352147; hg19: chr3-46414282;