rs41442546

Variant names:

• chr3-46375578-C-A
• rs41442546
• NM_001394783.1:c.*1617C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-46375578-C-A
• chr3-46375578-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394783.1(CCR5):​c.*1617C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 165,984 control chromosomes in the GnomAD database, including 77 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 0.027 (74 hom., cov: 30)
  • Exomes 𝑓: 0.013 (3 hom.)
• Consequence: CCR5 NM_001394783.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0268 (4050/151092) while in subpopulation NFE AF = 0.0423 (2869/67826). AF 95% confidence interval is 0.041. There are 74 homozygotes in GnomAd4. There are 1783 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4050 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.*1617C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.2	n.399-4161G>T		intron_variant	Intron 2 of 3	ENST00000451485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.*1617C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001394783.1	ENSP00000292303.4
CCR5AS	ENST00000451485.3	n.399-4161G>T		intron_variant	Intron 2 of 3	3	NR_125406.2

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4050 AN: 150970 Hom.: 74 Cov.: 30

Gnomad AFR AF: 0.00775

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0381

GnomAD4 exome AF: 0.0128 AC: 190 AN: 14892 Hom.: 3 Cov.: 0 AF XY: 0.0122 AC XY: 86 AN XY: 7072

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0127 AC: 187 AN: 14700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 88

Other (OTH) AF: 0.0333 AC: 3 AN: 90

GnomAD4 genome AF: 0.0268 AC: 4050 AN: 151092 Hom.: 74 Cov.: 30 AF XY: 0.0242 AC XY: 1783 AN XY: 73766

African (AFR) AF: 0.00773 AC: 318 AN: 41140

American (AMR) AF: 0.0298 AC: 450 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.0170 AC: 81 AN: 4756

European-Finnish (FIN) AF: 0.0139 AC: 145 AN: 10444

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0423 AC: 2869 AN: 67826

Other (OTH) AF: 0.0377 AC: 79 AN: 2098

Alfa AF: 0.0352 Hom.: 161

Bravo AF: 0.0279

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs41442546; hg19: chr3-46417069;