rs20572

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-36072675-C-A
• chr21-36072675-C-G
• chr21-36072675-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001757.4(CBR1):​c.627C>A​(p.Ala209Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR1	NM_001757.4	MANE Select	c.627C>A	p.Ala209Ala	synonymous	Exon 3 of 3	NP_001748.1
	CBR1	NM_001286789.2		c.*736C>A		3_prime_UTR	Exon 3 of 3	NP_001273718.1
	CBR1-AS1	NR_040084.1		n.378-2190G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBR1	ENST00000290349.11	TSL:1 MANE Select	c.627C>A	p.Ala209Ala	synonymous	Exon 3 of 3	ENSP00000290349.6
	CBR1	ENST00000530908.5	TSL:1	c.*736C>A		3_prime_UTR	Exon 3 of 3	ENSP00000434613.1
	SETD4	ENST00000399201.5	TSL:1	c.-203+6630G>T		intron	N/A	ENSP00000382152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		1.5

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;