chr2-72132272-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_019885.4(CYP26B1):​c.1494C>T​(p.Asn498Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,604,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CYP26B1
NM_019885.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.27
Variant links:
Genes affected
CYP26B1 (HGNC:20581): (cytochrome P450 family 26 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein is localized to the endoplasmic reticulum, and functions as a critical regulator of all-trans retinoic acid levels by the specific inactivation of all-trans retinoic acid to hydroxylated forms. Mutations in this gene are associated with radiohumeral fusions and other skeletal and craniofacial anomalies, and increased levels of the encoded protein are associated with atherosclerotic lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 2-72132272-G-A is Benign according to our data. Variant chr2-72132272-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3375393.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.27 with no splicing effect.
BS2
High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP26B1NM_019885.4 linkc.1494C>T p.Asn498Asn synonymous_variant Exon 6 of 6 ENST00000001146.7 NP_063938.1 Q9NR63-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP26B1ENST00000001146.7 linkc.1494C>T p.Asn498Asn synonymous_variant Exon 6 of 6 1 NM_019885.4 ENSP00000001146.2 Q9NR63-1
CYP26B1ENST00000546307.5 linkc.1269C>T p.Asn423Asn synonymous_variant Exon 5 of 5 1 ENSP00000443304.1 Q9NR63-2
CYP26B1ENST00000412253.1 linkc.921C>T p.Asn307Asn synonymous_variant Exon 5 of 5 1 ENSP00000401465.1 E7ER08

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000435
AC:
10
AN:
230090
Hom.:
0
AF XY:
0.0000322
AC XY:
4
AN XY:
124298
show subpopulations
Gnomad AFR exome
AF:
0.0000698
Gnomad AMR exome
AF:
0.000186
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000519
Gnomad NFE exome
AF:
0.0000193
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000337
AC:
49
AN:
1452788
Hom.:
0
Cov.:
32
AF XY:
0.0000319
AC XY:
23
AN XY:
721714
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000162
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.0000833
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000456
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

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

Submissions by phenotype

not specified Benign:1
Sep 18, 2024
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
13
DANN
Benign
0.78

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: rs140097862; hg19: chr2-72359401; API