NM_001394783.1:c.*1234A>G

Variant names:

• chr3-46375195-A-G
• rs41526948
• NM_001394783.1:c.*1234A>G

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.*1234A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 167,182 control chromosomes in the GnomAD database, including 31 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 0.012 (22 hom., cov: 30)
  • Exomes 𝑓: 0.033 (9 hom.)
• Consequence: CCR5 NM_001394783.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 4 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0124 (1888/152246) while in subpopulation NFE AF = 0.017 (1156/68018). AF 95% confidence interval is 0.0162. There are 22 homozygotes in GnomAd4. There are 1015 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1888 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	NM_001394783.1	MANE Select	c.*1234A>G		3_prime_UTR	Exon 2 of 2	NP_001381712.1	Q38L21
	CCR5AS	NR_125406.2	MANE Select	n.399-3778T>C		intron	N/A
	CCR5	NM_000579.4		c.*1234A>G		3_prime_UTR	Exon 3 of 3	NP_000570.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	ENST00000292303.5	TSL:1 MANE Select	c.*1234A>G		3_prime_UTR	Exon 2 of 2	ENSP00000292303.4	P51681
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-3778T>C		intron	N/A
	CCR5AS	ENST00000701879.2		n.289-3778T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1889 AN: 152128 Hom.: 22 Cov.: 30

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0331 AC: 494 AN: 14936 Hom.: 9 Cov.: 0 AF XY: 0.0341 AC XY: 242 AN XY: 7106

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0333 AC: 489 AN: 14698

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

European-Non Finnish (NFE) AF: 0.00794 AC: 1 AN: 126

Other (OTH) AF: 0.0417 AC: 4 AN: 96

GnomAD4 genome AF: 0.0124 AC: 1888 AN: 152246 Hom.: 22 Cov.: 30 AF XY: 0.0136 AC XY: 1015 AN XY: 74440

African (AFR) AF: 0.00325 AC: 135 AN: 41552

American (AMR) AF: 0.00987 AC: 151 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4818

European-Finnish (FIN) AF: 0.0313 AC: 332 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1156 AN: 68018

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.0154 Hom.: 34

Bravo AF: 0.00991

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.54
PhyloP100		-0.54
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: rs41526948; hg19: chr3-46416686; COSMIC: COSV52752168; COSMIC: COSV52752168;