Variant rs2230192 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_001757.4(CBR1):c.693G>A(p.Val231Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,614,130 control chromosomes in the GnomAD database, including 176 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 0.016 ( 22 hom., cov: 31)

Exomes 𝑓: 0.012 ( 154 hom. )

Consequence

CBR1
NM_001757.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

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:):

CBR1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=0.368 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0165 (2506/152246) while in subpopulation AMR AF= 0.024 (367/15294). AF 95% confidence interval is 0.022. There are 22 homozygotes in gnomad4. There are 1207 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBR1	NM_001757.4 linkuse as main transcript	c.693G>A	p.Val231Val	synonymous_variant	3/3	ENST00000290349.11	NP_001748.1	P16152-1A0A384NL53
CBR1	NM_001286789.2 linkuse as main transcript	c.*802G>A		3_prime_UTR_variant	3/3		NP_001273718.1	P16152-2
CBR1-AS1	NR_040084.1 linkuse as main transcript	n.377+2140C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBR1	ENST00000290349.11 linkuse as main transcript	c.693G>A	p.Val231Val	synonymous_variant	3/3	1	NM_001757.4	ENSP00000290349.6	P16152-1
CBR1	ENST00000530908.5 linkuse as main transcript	c.*802G>A		3_prime_UTR_variant	3/3	1		ENSP00000434613.1	P16152-2
SETD4	ENST00000399201.5 linkuse as main transcript	c.-203+6564C>T		intron_variant		1		ENSP00000382152.1	A8MTS1
CBR1-AS1	ENST00000535199.5 linkuse as main transcript	n.377+2140C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2509

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0129

AC:

3215

AN:

249818

Hom.:

AF XY:

0.0122

AC XY:

1644

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0122

AC:

17835

AN:

1461884

Hom.:

154

Cov.:

AF XY:

0.0121

AC XY:

8771

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0215

Gnomad4 AMR exome

AF:

0.0186

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.0164

GnomAD4 genome

AF:

0.0165

AC:

2506

AN:

152246

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1207

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0207

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0147

EpiControl

AF:

0.0141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.9

DANN

Benign

0.80

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