rs10853744

Variant names:

• chr19-41016034-G-T
• rs10853744
• NM_000767.5:c.1295-612G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.1295-612G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 136,234 control chromosomes in the GnomAD database, including 7,026 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 0.33 (7026 hom., cov: 29)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1295-612G>T		intron_variant	Intron 8 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1295-612G>T		intron_variant	Intron 8 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.648-612G>T		intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1	c.587-612G>T		intron_variant	Intron 4 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*652-612G>T		intron_variant	Intron 9 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 44728 AN: 136144 Hom.: 7026 Cov.: 29

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.328 AC: 44746 AN: 136234 Hom.: 7026 Cov.: 29 AF XY: 0.330 AC XY: 21860 AN XY: 66204

African (AFR) AF: 0.440 AC: 15389 AN: 34982

American (AMR) AF: 0.391 AC: 5335 AN: 13640

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 972 AN: 3244

East Asian (EAS) AF: 0.239 AC: 1065 AN: 4448

South Asian (SAS) AF: 0.435 AC: 1905 AN: 4384

European-Finnish (FIN) AF: 0.224 AC: 2059 AN: 9206

Middle Eastern (MID) AF: 0.357 AC: 97 AN: 272

European-Non Finnish (NFE) AF: 0.271 AC: 17171 AN: 63342

Other (OTH) AF: 0.349 AC: 654 AN: 1872

Alfa AF: 0.287 Hom.: 1848

Bravo AF: 0.306

Asia WGS AF: 0.325 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.29
PhyloP100		-0.98
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: rs10853744; hg19: chr19-41521939;