rs25678

Variant names:

• chr21-36070334-G-C
• rs25678
• NM_001757.4:c.219G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-36070334-G-C
• chr21-36070334-G-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.219G>C​(p.Leu73Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,613,098 control chromosomes in the GnomAD database, including 18,366 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 0.13 (1492 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16874 hom.)
• Consequence: CBR1 NM_001757.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 22 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]

ENSG00000289001 (HGNC:):

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=-0.36).
• BP7: Synonymous conserved (PhyloP=0.217 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBR1	NM_001757.4	c.219G>C	p.Leu73Leu	synonymous_variant	Exon 1 of 3	ENST00000290349.11	NP_001748.1
CBR1	NM_001286789.2	c.219G>C	p.Leu73Leu	synonymous_variant	Exon 1 of 3		NP_001273718.1
CBR1-AS1	NR_040084.1	n.529C>G		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBR1	ENST00000290349.11	c.219G>C	p.Leu73Leu	synonymous_variant	Exon 1 of 3	1	NM_001757.4	ENSP00000290349.6

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20399 AN: 152128 Hom.: 1491 Cov.: 32

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.160 AC: 39606 AN: 247188 AF XY: 0.163

Gnomad AFR exome AF: 0.0905

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.147 AC: 215214 AN: 1460852 Hom.: 16874 Cov.: 32 AF XY: 0.150 AC XY: 108985 AN XY: 726752

African (AFR) AF: 0.0843 AC: 2821 AN: 33466

American (AMR) AF: 0.204 AC: 9123 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3833 AN: 26120

East Asian (EAS) AF: 0.241 AC: 9579 AN: 39680

South Asian (SAS) AF: 0.235 AC: 20286 AN: 86232

European-Finnish (FIN) AF: 0.131 AC: 6902 AN: 52648

Middle Eastern (MID) AF: 0.115 AC: 663 AN: 5768

European-Non Finnish (NFE) AF: 0.138 AC: 153146 AN: 1111868

Other (OTH) AF: 0.147 AC: 8861 AN: 60374

GnomAD4 genome AF: 0.134 AC: 20391 AN: 152246 Hom.: 1492 Cov.: 32 AF XY: 0.135 AC XY: 10046 AN XY: 74446

African (AFR) AF: 0.0896 AC: 3725 AN: 41570

American (AMR) AF: 0.167 AC: 2555 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1091 AN: 5154

South Asian (SAS) AF: 0.231 AC: 1112 AN: 4820

European-Finnish (FIN) AF: 0.142 AC: 1507 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9559 AN: 67992

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.139 Hom.: 515

Bravo AF: 0.131

Asia WGS AF: 0.221 AC: 768 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		0.22
PromoterAI		-0.021	Neutral
Mutation Taster		=98/2	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: rs25678; hg19: chr21-37442632; COSMIC: COSV51738457; COSMIC: COSV51738457;