chr21-36071595-T-C

Variant names:

• chr21-36071595-T-C
• rs3787728
• NM_001757.4:c.397+538T>C

Variant summary

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

The NM_001757.4(CBR1):​c.397+538T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 575,842 control chromosomes in the GnomAD database, including 150,389 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 0.74 (41466 hom., cov: 30)
  • Exomes 𝑓: 0.71 (108923 hom.)
• Consequence: CBR1 NM_001757.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 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.397+538T>C		intron	N/A	NP_001748.1	P16152-1
	CBR1	NM_001286789.2		c.398-220T>C		intron	N/A	NP_001273718.1	P16152-2
	CBR1-AS1	NR_040084.1		n.378-1110A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR1	ENST00000290349.11	TSL:1 MANE Select	c.397+538T>C		intron	N/A	ENSP00000290349.6	P16152-1
	SETD4	ENST00000399201.5	TSL:1	c.-203+7710A>G		intron	N/A	ENSP00000382152.1	A8MTS1
	CBR1	ENST00000530908.5	TSL:1	c.398-220T>C		intron	N/A	ENSP00000434613.1	P16152-2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111853 AN: 151738 Hom.: 41421 Cov.: 30

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.714 AC: 302602 AN: 423986 Hom.: 108923 Cov.: 2 AF XY: 0.720 AC XY: 160424 AN XY: 222884

African (AFR) AF: 0.801 AC: 9613 AN: 12006

American (AMR) AF: 0.759 AC: 12661 AN: 16692

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 9002 AN: 13118

East Asian (EAS) AF: 0.568 AC: 16936 AN: 29840

South Asian (SAS) AF: 0.815 AC: 33840 AN: 41516

European-Finnish (FIN) AF: 0.708 AC: 19960 AN: 28204

Middle Eastern (MID) AF: 0.772 AC: 1435 AN: 1860

European-Non Finnish (NFE) AF: 0.709 AC: 181451 AN: 255912

Other (OTH) AF: 0.713 AC: 17704 AN: 24838

GnomAD4 genome AF: 0.737 AC: 111955 AN: 151856 Hom.: 41466 Cov.: 30 AF XY: 0.739 AC XY: 54868 AN XY: 74200

African (AFR) AF: 0.797 AC: 33000 AN: 41408

American (AMR) AF: 0.750 AC: 11443 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2357 AN: 3466

East Asian (EAS) AF: 0.544 AC: 2795 AN: 5142

South Asian (SAS) AF: 0.810 AC: 3897 AN: 4810

European-Finnish (FIN) AF: 0.734 AC: 7737 AN: 10538

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48410 AN: 67926

Other (OTH) AF: 0.725 AC: 1528 AN: 2108

Alfa AF: 0.717 Hom.: 75948

Bravo AF: 0.736

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.0
DANN	Benign	0.48
PhyloP100		-0.061
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: rs3787728; hg19: chr21-37443893;