Variant chr21-36072675-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001757.4(CBR1):c.627C>T(p.Ala209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,804 control chromosomes in the GnomAD database, including 13,817 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 ( 1023 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12794 hom. )

Consequence

CBR1
NM_001757.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Variant links:

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]

CBR1 links:

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]

SETD4 links:

CBR1-AS1 (HGNC:55777): (CBR1 antisense RNA 1)

CBR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CBR1	NM_001757.4 linkuse as main transcript	c.627C>T	p.Ala209=	synonymous_variant	3/3	ENST00000290349.11
CBR1-AS1	NR_040084.1 linkuse as main transcript	n.378-2190G>A		intron_variant, non_coding_transcript_variant
CBR1	NM_001286789.2 linkuse as main transcript	c.*736C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBR1	ENST00000290349.11 linkuse as main transcript	c.627C>T	p.Ala209=	synonymous_variant	3/3	1	NM_001757.4	P1	P16152-1
CBR1	ENST00000530908.5 linkuse as main transcript	c.*736C>T		3_prime_UTR_variant	3/3	1			P16152-2
SETD4	ENST00000399201.5 linkuse as main transcript	c.-203+6630G>A		intron_variant		1
CBR1-AS1	ENST00000535199.5 linkuse as main transcript	n.378-2190G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15341

AN:

152050

Hom.:

1022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0629

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0954

GnomAD3 exomes

AF:

0.135

AC:

33629

AN:

249182

Hom.:

2692

AF XY:

0.137

AC XY:

18444

AN XY:

134908

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.0651

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:

184708

AN:

1461636

Hom.:

12794

Cov.:

AF XY:

0.128

AC XY:

93036

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.0663

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:

15342

AN:

152168

Hom.:

1023

Cov.:

AF XY:

0.102

AC XY:

7564

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.0629

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.0972

Alfa

AF:

0.115

Hom.:

2220

Bravo

AF:

0.0959

Asia WGS

AF:

0.228

AC:

790

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_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over