rs2835265

Positions:

• chr21-36072398-C-T

Variant summary

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

The NM_001286789.2(CBR1):​c.*459C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,512 control chromosomes in the GnomAD database, including 13,828 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 0.10 (1028 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12800 hom.)
• Consequence: CBR1 NM_001286789.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

CBR1 (HGNC:1548): (carbonyl reductase 1) The protein encoded by this gene belongs to the short-chain dehydrogenases/reductases (SDR) family, which function as NADPH-dependent oxidoreductases having wide specificity for carbonyl compounds, such as quinones, prostaglandins, and various xenobiotics. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CBR1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034991503).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBR1	NM_001757.4	c.398-48C>T		intron_variant		ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2	c.*459C>T		3_prime_UTR_variant	3/3		NP_001273718.1
CBR1-AS1	NR_040084.1	n.378-1913G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11	c.398-48C>T		intron_variant		1	NM_001757.4	ENSP00000290349.6

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15364 AN: 152116 Hom.: 1026 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0958

GnomAD3 exomes AF: 0.135 AC: 33534 AN: 248080 Hom.: 2695 AF XY: 0.137 AC XY: 18415 AN XY: 134536

Gnomad AFR exome AF: 0.0256

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.0649

Gnomad EAS exome AF: 0.200

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.126 AC: 184688 AN: 1461278 Hom.: 12800 Cov.: 33 AF XY: 0.128 AC XY: 93037 AN XY: 726996

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.101 AC: 15372 AN: 152234 Hom.: 1028 Cov.: 32 AF XY: 0.102 AC XY: 7584 AN XY: 74408

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.112 Hom.: 1405

Bravo AF: 0.0960

TwinsUK AF: 0.128 AC: 474

ALSPAC AF: 0.124 AC: 478

ESP6500AA AF: 0.0247 AC: 109

ESP6500EA AF: 0.117 AC: 1009

ExAC AF: 0.133 AC: 16086

Asia WGS AF: 0.229 AC: 795 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.3
DANN	Benign	0.62
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	0.031	D
Vest4		0.082
ClinPred		0.0029	T
GERP RS		-6.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835265; hg19: chr21-37444696; COSMIC: COSV51738315; COSMIC: COSV51738315;