rs9024

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-36073015-G-A
• chr21-36073015-G-C
• chr21-36073015-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBR1	NM_001757.4	c.*133G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2	c.*1076G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1	n.377+1866C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11	c.*133G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001757.4	ENSP00000290349.6
CBR1	ENST00000530908.5	c.*1076G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000434613.1
SETD4	ENST00000399201.5	c.-203+6290C>T		intron_variant	Intron 1 of 7	1		ENSP00000382152.1
CBR1-AS1	ENST00000535199.5	n.377+1866C>T		intron_variant	Intron 3 of 3	2

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

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.0729

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.120

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

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.117 Hom.: 2274

Bravo AF: 0.0961

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs9024; hg19: chr21-37445313;