chr3-46370444-A-G

Position:

• chr3-46370444-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_125406.1(CCR5AS):​n.565+800T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,794 control chromosomes in the GnomAD database, including 18,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,protective (no stars).

• Frequency: Genomes: 𝑓 0.49 (18573 hom., cov: 30)
• Consequence: CCR5AS NR_125406.1 intron, non_coding_transcript
• Clinical Significance: Conflicting classifications of pathogenicity; protective no assertion criteria provided P:1 B:3
• Conservation: PhyloP100: -0.587

Genes affected

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

CCR5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5AS	NR_125406.1	n.565+800T>C		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-301+246A>G		intron_variant			NP_000570.1
CCR5	NM_001100168.2	c.-66+246A>G		intron_variant			NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5AS	ENST00000701879.1	n.347+800T>C		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.565+800T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74529 AN: 151674 Hom.: 18552 Cov.: 30

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.491 AC: 74586 AN: 151794 Hom.: 18573 Cov.: 30 AF XY: 0.496 AC XY: 36779 AN XY: 74166

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.492

Alfa AF: 0.458 Hom.: 3595

Bravo AF: 0.493

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity; protective

Submissions summary: Pathogenic:1 Benign:3

Revision: no assertion criteria provided

Submissions by phenotype

Acquired immunodeficiency syndrome, delayed progression to Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2003

- -

CCR5-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Susceptibility to HIV infection Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jul 08, 2003

- -

CCR5 PROMOTER POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 08, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799987; hg19: chr3-46411935;