Variant 21-36072639-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001757.4(CBR1):c.591G>A(p.Thr197Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,611,506 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 5 hom. )

Consequence

CBR1
NM_001757.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.902

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 21-36072639-G-A is Benign according to our data. Variant chr21-36072639-G-A is described in ClinVar as [Benign]. Clinvar id is 714831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.902 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBR1	NM_001757.4 linkuse as main transcript	c.591G>A	p.Thr197Thr	synonymous_variant	3/3	ENST00000290349.11	NP_001748.1	P16152-1A0A384NL53
CBR1	NM_001286789.2 linkuse as main transcript	c.*700G>A		3_prime_UTR_variant	3/3		NP_001273718.1	P16152-2
CBR1-AS1	NR_040084.1 linkuse as main transcript	n.378-2154C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBR1	ENST00000290349.11 linkuse as main transcript	c.591G>A	p.Thr197Thr	synonymous_variant	3/3	1	NM_001757.4	ENSP00000290349.6	P16152-1
CBR1	ENST00000530908.5 linkuse as main transcript	c.*700G>A		3_prime_UTR_variant	3/3	1		ENSP00000434613.1	P16152-2
SETD4	ENST00000399201.5 linkuse as main transcript	c.-203+6666C>T		intron_variant		1		ENSP00000382152.1	A8MTS1
CBR1-AS1	ENST00000535199.5 linkuse as main transcript	n.378-2154C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00473

AC:

720

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00175

AC:

435

AN:

247962

Hom.:

AF XY:

0.00144

AC XY:

193

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00205

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000755

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000583

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000972

AC:

1419

AN:

1459238

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

645

AN XY:

725740

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000592

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000480

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00482

AC:

734

AN:

152268

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

350

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00152

Hom.:

Bravo

AF:

0.00519

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.098

DANN

Benign

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over