chr21-36134867-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000453159.7(CBR3-AS1):​n.271-1793T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 155,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000064 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A
	CBR3-AS1	NR_038893.1		n.193-1793T>C		intron	N/A
	CBR3	NM_001236.4	MANE Select	c.-326A>G		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>C		intron	N/A
	CBR3-AS1	ENST00000625189.3	TSL:5	n.7T>C		non_coding_transcript_exon	Exon 1 of 2
	CBR3-AS1	ENST00000661388.1		n.553T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000645 AC: 10 AN: 155090 Hom.: 0 Cov.: 2 AF XY: 0.0000776 AC XY: 6 AN XY: 77276

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000188 AC: 1 AN: 5320

American (AMR) AF: 0.00 AC: 0 AN: 4604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6560

East Asian (EAS) AF: 0.00 AC: 0 AN: 14000

South Asian (SAS) AF: 0.00 AC: 0 AN: 2336

European-Finnish (FIN) AF: 0.0000919 AC: 1 AN: 10876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 828

European-Non Finnish (NFE) AF: 0.0000804 AC: 8 AN: 99448

Other (OTH) AF: 0.00 AC: 0 AN: 11118

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.61
PhyloP100		-4.2
PromoterAI		0.0082	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;