chr21-36072675-C-T

Variant names:

• chr21-36072675-C-T
• rs20572
• NM_001757.4:c.627C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001757.4(CBR1):​c.627C>T​(p.Ala209Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,804 control chromosomes in the GnomAD database, including 13,817 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 (1023 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12794 hom.)
• Consequence: CBR1 NM_001757.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 38 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.
• 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.627C>T	p.Ala209Ala	synonymous_variant	Exon 3 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2	c.*736C>T		3_prime_UTR_variant	Exon 3 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1	n.378-2190G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11	c.627C>T	p.Ala209Ala	synonymous_variant	Exon 3 of 3	1	NM_001757.4	ENSP00000290349.6
CBR1	ENST00000530908.5	c.*736C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000434613.1
SETD4	ENST00000399201.5	c.-203+6630G>A		intron_variant	Intron 1 of 7	1		ENSP00000382152.1
CBR1	ENST00000399191.3	c.*230C>T		downstream_gene_variant		3		ENSP00000382143.3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15341 AN: 152050 Hom.: 1022 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0954

GnomAD2 exomes AF: 0.135 AC: 33629 AN: 249182 AF XY: 0.137

Gnomad AFR exome AF: 0.0251

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.126 AC: 184708 AN: 1461636 Hom.: 12794 Cov.: 34 AF XY: 0.128 AC XY: 93036 AN XY: 727124

African (AFR) AF: 0.0192 AC: 644 AN: 33474

American (AMR) AF: 0.189 AC: 8427 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 1731 AN: 26116

East Asian (EAS) AF: 0.242 AC: 9591 AN: 39698

South Asian (SAS) AF: 0.184 AC: 15864 AN: 86242

European-Finnish (FIN) AF: 0.123 AC: 6558 AN: 53418

Middle Eastern (MID) AF: 0.0723 AC: 417 AN: 5766

European-Non Finnish (NFE) AF: 0.121 AC: 134229 AN: 1111864

Other (OTH) AF: 0.120 AC: 7247 AN: 60386

GnomAD4 genome AF: 0.101 AC: 15342 AN: 152168 Hom.: 1023 Cov.: 32 AF XY: 0.102 AC XY: 7564 AN XY: 74394

African (AFR) AF: 0.0242 AC: 1006 AN: 41546

American (AMR) AF: 0.143 AC: 2185 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3464

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5152

South Asian (SAS) AF: 0.179 AC: 860 AN: 4812

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10604

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

European-Non Finnish (NFE) AF: 0.122 AC: 8318 AN: 68006

Other (OTH) AF: 0.0972 AC: 205 AN: 2108

Alfa AF: 0.115 Hom.: 4940

Bravo AF: 0.0959

Asia WGS AF: 0.228 AC: 790 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		1.5
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: rs20572; hg19: chr21-37444973; COSMIC: COSV51738338; COSMIC: COSV51738338;