Variant 2-72132389-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019885.4(CYP26B1):c.1377T>C(p.Ala459=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 1,610,962 control chromosomes in the GnomAD database, including 5,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1298 hom., cov: 33)

Exomes 𝑓: 0.057 ( 3987 hom. )

Consequence

CYP26B1
NM_019885.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.97

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]

CYP26B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 2-72132389-A-G is Benign according to our data. Variant chr2-72132389-A-G is described in ClinVar as [Benign]. Clinvar id is 1266263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26B1	NM_019885.4 linkuse as main transcript	c.1377T>C	p.Ala459=	synonymous_variant	6/6	ENST00000001146.7	NP_063938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26B1	ENST00000001146.7 linkuse as main transcript	c.1377T>C	p.Ala459=	synonymous_variant	6/6	1	NM_019885.4	ENSP00000001146	P1	Q9NR63-1
CYP26B1	ENST00000546307.5 linkuse as main transcript	c.1152T>C	p.Ala384=	synonymous_variant	5/5	1		ENSP00000443304		Q9NR63-2
CYP26B1	ENST00000412253.1 linkuse as main transcript	c.804T>C	p.Ala268=	synonymous_variant	5/5	1		ENSP00000401465

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15450

AN:

152104

Hom.:

1281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0451

Gnomad OTH

AF:

0.0867

GnomAD3 exomes

AF:

0.0844

AC:

20830

AN:

246832

Hom.:

1821

AF XY:

0.0748

AC XY:

10025

AN XY:

134106

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.0612

Gnomad EAS exome

AF:

0.0468

Gnomad SAS exome

AF:

0.0506

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0688

GnomAD4 exome

AF:

0.0574

AC:

83711

AN:

1458740

Hom.:

3987

Cov.:

AF XY:

0.0558

AC XY:

40472

AN XY:

725326

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.0612

Gnomad4 EAS exome

AF:

0.0472

Gnomad4 SAS exome

AF:

0.0532

Gnomad4 FIN exome

AF:

0.0350

Gnomad4 NFE exome

AF:

0.0462

Gnomad4 OTH exome

AF:

0.0651

GnomAD4 genome

AF:

0.102

AC:

15496

AN:

152222

Hom.:

1298

Cov.:

AF XY:

0.0995

AC XY:

7403

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.0526

Gnomad4 SAS

AF:

0.0530

Gnomad4 FIN

AF:

0.0323

Gnomad4 NFE

AF:

0.0451

Gnomad4 OTH

AF:

0.0853

Alfa

AF:

0.0685

Hom.:

302

Bravo

AF:

0.118

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

EpiCase

AF:

0.0428

EpiControl

AF:

0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.4

DANN

Benign

0.69

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over