chr21-36134867-A-T

Variant names:

• chr21-36134867-A-T
• rs8132243
• ENST00000453159.7:n.271-1793T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000453159.7(CBR3-AS1):​n.271-1793T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 307,058 control chromosomes in the GnomAD database, including 119,138 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 0.89 (59916 hom., cov: 32)
  • Exomes 𝑓: 0.87 (59222 hom.)
• Consequence: CBR3-AS1 ENST00000453159.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.24
• Publications: 6 publications found

Genes affected

CBR3-AS1 (HGNC:43664): (CBR3 antisense RNA 1)

CBR3 (HGNC:1549): (carbonyl reductase 3) Carbonyl reductase 3 catalyzes the reduction of a large number of biologically and pharmacologically active carbonyl compounds to their corresponding alcohols. The enzyme is classified as a monomeric NADPH-dependent oxidoreductase. CBR3 contains three exons spanning 11.2 kilobases and is closely linked to another carbonyl reductase gene - CBR1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453159.7. 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
	CBR3-AS1	NR_038892.1		n.193-1106T>A		intron	N/A
	CBR3-AS1	NR_038893.1		n.193-1793T>A		intron	N/A
	CBR3	NM_001236.4	MANE Select	c.-326A>T		upstream_gene	N/A	NP_001227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR3-AS1	ENST00000453159.7	TSL:1	n.271-1793T>A		intron	N/A
	CBR3-AS1	ENST00000625189.3	TSL:5	n.7T>A		non_coding_transcript_exon	Exon 1 of 2
	CBR3-AS1	ENST00000661388.1		n.553T>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134810 AN: 152106 Hom.: 59872 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.874 AC: 135256 AN: 154836 Hom.: 59222 Cov.: 2 AF XY: 0.876 AC XY: 67573 AN XY: 77146

African (AFR) AF: 0.943 AC: 5014 AN: 5318

American (AMR) AF: 0.836 AC: 3841 AN: 4592

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 5953 AN: 6550

East Asian (EAS) AF: 0.835 AC: 11670 AN: 13974

South Asian (SAS) AF: 0.867 AC: 2024 AN: 2334

European-Finnish (FIN) AF: 0.785 AC: 8502 AN: 10828

Middle Eastern (MID) AF: 0.894 AC: 740 AN: 828

European-Non Finnish (NFE) AF: 0.884 AC: 87767 AN: 99308

Other (OTH) AF: 0.878 AC: 9745 AN: 11104

GnomAD4 genome AF: 0.886 AC: 134909 AN: 152222 Hom.: 59916 Cov.: 32 AF XY: 0.881 AC XY: 65565 AN XY: 74404

African (AFR) AF: 0.943 AC: 39174 AN: 41560

American (AMR) AF: 0.843 AC: 12888 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3132 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4376 AN: 5172

South Asian (SAS) AF: 0.867 AC: 4182 AN: 4824

European-Finnish (FIN) AF: 0.797 AC: 8437 AN: 10580

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.880 AC: 59841 AN: 68006

Other (OTH) AF: 0.888 AC: 1876 AN: 2112

Alfa AF: 0.825 Hom.: 2511

Bravo AF: 0.893

Asia WGS AF: 0.830 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-4.2
PromoterAI		-0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs8132243; hg19: chr21-37507165;