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GeneBe

21-36072741-G-A

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.Val231=) 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

2

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]
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:55777): (CBR1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.368 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CBR1NM_001757.4 linkuse as main transcriptc.693G>A p.Val231= synonymous_variant 3/3 ENST00000290349.11
CBR1-AS1NR_040084.1 linkuse as main transcriptn.377+2140C>T intron_variant, non_coding_transcript_variant
CBR1NM_001286789.2 linkuse as main transcriptc.*802G>A 3_prime_UTR_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CBR1ENST00000290349.11 linkuse as main transcriptc.693G>A p.Val231= synonymous_variant 3/31 NM_001757.4 P1P16152-1
CBR1ENST00000530908.5 linkuse as main transcriptc.*802G>A 3_prime_UTR_variant 3/31 P16152-2
SETD4ENST00000399201.5 linkuse as main transcriptc.-203+6564C>T intron_variant 1
CBR1-AS1ENST00000535199.5 linkuse as main transcriptn.377+2140C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0165
AC:
2509
AN:
152128
Hom.:
22
Cov.:
31
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.:
44
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.:
33
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0165
AC:
2506
AN:
152246
Hom.:
22
Cov.:
31
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.:
36
Bravo
AF:
0.0178
Asia WGS
AF:
0.00318
AC:
11
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.

Other links and lift over

dbSNP: rs2230192; hg19: chr21-37445039; API