chr22-42141910-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000433992.2(CYP2D7):​c.802A>C​(p.Thr268Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,610,476 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 31 hom. )

Consequence

CYP2D7
ENST00000433992.2 missense

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13
Variant links:
Genes affected
CYP2D7 (HGNC:2624): (cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)) This gene is a member of the cytochrome P450 gene superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is a segregating pseudogene, where some individuals may have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional. In this case, the functional allele is thought to be rare. This locus is part of a cluster of cytochrome P450 genes on chromosome 22. [provided by RefSeq, Jan 2017]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 22-42141910-T-G is Benign according to our data. Variant chr22-42141910-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653243.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00225 (3276/1458314) while in subpopulation MID AF = 0.0202 (116/5754). AF 95% confidence interval is 0.0172. There are 31 homozygotes in GnomAdExome4. There are 1675 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP2D7NR_002570.6 linkn.821A>C non_coding_transcript_exon_variant Exon 5 of 9
CYP2D7NR_145674.3 linkn.821A>C non_coding_transcript_exon_variant Exon 5 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2D7ENST00000433992.2 linkc.802A>C p.Thr268Pro missense_variant Exon 5 of 9 1 ENSP00000439604.1

Frequencies

GnomAD3 genomes
AF:
0.00363
AC:
552
AN:
152044
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00587
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.00386
Gnomad ASJ
AF:
0.0306
Gnomad EAS
AF:
0.00155
Gnomad SAS
AF:
0.00395
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.00134
Gnomad OTH
AF:
0.00431
GnomAD2 exomes
AF:
0.00332
AC:
818
AN:
246470
AF XY:
0.00332
show subpopulations
Gnomad AFR exome
AF:
0.00466
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.0326
Gnomad EAS exome
AF:
0.000386
Gnomad FIN exome
AF:
0.000328
Gnomad NFE exome
AF:
0.00168
Gnomad OTH exome
AF:
0.00514
GnomAD4 exome
AF:
0.00225
AC:
3276
AN:
1458314
Hom.:
31
Cov.:
34
AF XY:
0.00231
AC XY:
1675
AN XY:
725194
show subpopulations
Gnomad4 AFR exome
AF:
0.00706
AC:
236
AN:
33416
Gnomad4 AMR exome
AF:
0.00275
AC:
122
AN:
44392
Gnomad4 ASJ exome
AF:
0.0317
AC:
826
AN:
26034
Gnomad4 EAS exome
AF:
0.00680
AC:
269
AN:
39570
Gnomad4 SAS exome
AF:
0.00277
AC:
236
AN:
85194
Gnomad4 FIN exome
AF:
0.000395
AC:
21
AN:
53206
Gnomad4 NFE exome
AF:
0.00106
AC:
1173
AN:
1110516
Gnomad4 Remaining exome
AF:
0.00460
AC:
277
AN:
60232
Heterozygous variant carriers
0
160
320
481
641
801
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
56
112
168
224
280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00361
AC:
550
AN:
152162
Hom.:
4
Cov.:
33
AF XY:
0.00370
AC XY:
275
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.00587
AC:
0.00587499
AN:
0.00587499
Gnomad4 AMR
AF:
0.00386
AC:
0.00385722
AN:
0.00385722
Gnomad4 ASJ
AF:
0.0306
AC:
0.0305828
AN:
0.0305828
Gnomad4 EAS
AF:
0.00155
AC:
0.00155159
AN:
0.00155159
Gnomad4 SAS
AF:
0.00395
AC:
0.0039501
AN:
0.0039501
Gnomad4 FIN
AF:
0.000471
AC:
0.000470898
AN:
0.000470898
Gnomad4 NFE
AF:
0.00132
AC:
0.00132415
AN:
0.00132415
Gnomad4 OTH
AF:
0.00427
AC:
0.0042654
AN:
0.0042654
Heterozygous variant carriers
0
25
50
76
101
126
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00852
Hom.:
1
Bravo
AF:
0.00393

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Feb 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

CYP2D7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.75
DANN
Benign
0.73

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199515619; hg19: chr22-42537920; API