21-36073015-G-A

Variant names:

• chr21-36073015-G-A
• rs9024
• NM_001757.4:c.*133G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001757.4(CBR1):​c.*133G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 597,352 control chromosomes in the GnomAD database, including 5,455 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 (1027 hom., cov: 32)
  • Exomes 𝑓: 0.13 (4428 hom.)
• Consequence: CBR1 NM_001757.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 54 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001757.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR1	NM_001757.4	MANE Select	c.*133G>A		3_prime_UTR	Exon 3 of 3	NP_001748.1	P16152-1
	CBR1	NM_001286789.2		c.*1076G>A		3_prime_UTR	Exon 3 of 3	NP_001273718.1	P16152-2
	CBR1-AS1	NR_040084.1		n.377+1866C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR1	ENST00000290349.11	TSL:1 MANE Select	c.*133G>A		3_prime_UTR	Exon 3 of 3	ENSP00000290349.6	P16152-1
	CBR1	ENST00000530908.5	TSL:1	c.*1076G>A		3_prime_UTR	Exon 3 of 3	ENSP00000434613.1	P16152-2
	SETD4	ENST00000399201.5	TSL:1	c.-203+6290C>T		intron	N/A	ENSP00000382152.1	A8MTS1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15389 AN: 152122 Hom.: 1025 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0958

GnomAD4 exome AF: 0.133 AC: 59205 AN: 445112 Hom.: 4428 Cov.: 6 AF XY: 0.135 AC XY: 31219 AN XY: 230844

African (AFR) AF: 0.0243 AC: 296 AN: 12170

American (AMR) AF: 0.179 AC: 2713 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 942 AN: 12918

East Asian (EAS) AF: 0.254 AC: 7520 AN: 29610

South Asian (SAS) AF: 0.196 AC: 6730 AN: 34256

European-Finnish (FIN) AF: 0.129 AC: 3564 AN: 27710

Middle Eastern (MID) AF: 0.0765 AC: 147 AN: 1922

European-Non Finnish (NFE) AF: 0.120 AC: 34241 AN: 286046

Other (OTH) AF: 0.120 AC: 3052 AN: 25352

GnomAD4 genome AF: 0.101 AC: 15396 AN: 152240 Hom.: 1027 Cov.: 32 AF XY: 0.102 AC XY: 7599 AN XY: 74446

African (AFR) AF: 0.0245 AC: 1016 AN: 41546

American (AMR) AF: 0.143 AC: 2194 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5180

South Asian (SAS) AF: 0.179 AC: 864 AN: 4828

European-Finnish (FIN) AF: 0.132 AC: 1398 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8333 AN: 68004

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.116 Hom.: 4860

Bravo AF: 0.0961

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.61
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9024; hg19: chr21-37445313; COSMIC: COSV107328598; COSMIC: COSV107328598;