rs7250601

Positions:

• chr19-40997499-A-C
• chr19-40997499-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.171+6023A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,936 control chromosomes in the GnomAD database, including 7,168 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 0.30 (7168 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

Genes affected

CYP2B6 (HGNC:2615): (cytochrome P450 family 2 subfamily B member 6) This gene, CYP2B6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.171+6023A>C		intron_variant		ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.171+6023A>C		intron_variant		1	NM_000767.5	ENSP00000324648	P1
CYP2B6	ENST00000598834.2	c.73+6023A>C		intron_variant, NMD_transcript_variant		5		ENSP00000496294

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44804 AN: 151818 Hom.: 7167 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44824 AN: 151936 Hom.: 7168 Cov.: 31 AF XY: 0.295 AC XY: 21889 AN XY: 74268

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.311

Alfa AF: 0.197 Hom.: 717

Bravo AF: 0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.60

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: rs7250601; hg19: chr19-41503404;