19-40997499-A-C

Variant names:

• chr19-40997499-A-C
• rs7250601
• NM_000767.5:c.171+6023A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.171+6023A>C		intron_variant	Intron 1 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.171+6023A>C		intron_variant	Intron 1 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.72+6023A>C		intron_variant	Intron 1 of 9	5		ENSP00000496294.1

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

African (AFR) AF: 0.389 AC: 16074 AN: 41368

American (AMR) AF: 0.352 AC: 5365 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5184

South Asian (SAS) AF: 0.399 AC: 1918 AN: 4808

European-Finnish (FIN) AF: 0.185 AC: 1950 AN: 10552

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16817 AN: 67982

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.221 Hom.: 1033

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
PhyloP100		0.81
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: rs7250601; hg19: chr19-41503404;