chr19-40997499-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000767.5(CYP2B6):​c.171+6023A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 152,008 control chromosomes in the GnomAD database, including 12 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 0.0025 (12 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).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00248 (377/152008) while in subpopulation EAS AF = 0.0532 (276/5186). AF 95% confidence interval is 0.0481. There are 12 homozygotes in GnomAd4. There are 218 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 377 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 376 AN: 151890 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00474

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00248 AC: 377 AN: 152008 Hom.: 12 Cov.: 31 AF XY: 0.00293 AC XY: 218 AN XY: 74302

African (AFR) AF: 0.000121 AC: 5 AN: 41396

American (AMR) AF: 0.000131 AC: 2 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.0532 AC: 276 AN: 5186

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4810

European-Finnish (FIN) AF: 0.00474 AC: 50 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68008

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.0000314 Hom.: 1033

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.60
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

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;