rs41290186

Variant names:

• chr10-93075818-A-G
• rs41290186
• NM_000783.4:c.865-8A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-93075818-A-G
• chr10-93075818-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000783.4(CYP26A1):​c.865-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,609,298 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (33 hom.)
• Consequence: CYP26A1 NM_000783.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003761
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.524
• Publications: 3 publications found

Genes affected

CYP26A1 (HGNC:2603): (cytochrome P450 family 26 subfamily A member 1) This gene 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 endoplasmic reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

ENSG00000285846 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-93075818-A-G is Benign according to our data. Variant chr10-93075818-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640682.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP26A1	NM_000783.4	MANE Select	c.865-8A>G		splice_region intron	N/A	NP_000774.2
	CYP26A1	NM_057157.2		c.658-8A>G		splice_region intron	N/A	NP_476498.1	O43174-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP26A1	ENST00000224356.5	TSL:1 MANE Select	c.865-8A>G		splice_region intron	N/A	ENSP00000224356.4	O43174-1
	CYP26A1	ENST00000371531.5	TSL:2	c.658-8A>G		splice_region intron	N/A	ENSP00000360586.1	O43174-2
	CYP26A1	ENST00000623162.1	TSL:2	n.190A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 587 AN: 152106 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00656

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00386 AC: 971 AN: 251376 AF XY: 0.00394

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00617

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00616 AC: 8976 AN: 1457074 Hom.: 33 Cov.: 28 AF XY: 0.00596 AC XY: 4321 AN XY: 725260

African (AFR) AF: 0.000929 AC: 31 AN: 33380

American (AMR) AF: 0.00302 AC: 135 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00165 AC: 43 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00204 AC: 176 AN: 86150

European-Finnish (FIN) AF: 0.00223 AC: 119 AN: 53404

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5754

European-Non Finnish (NFE) AF: 0.00731 AC: 8092 AN: 1107622

Other (OTH) AF: 0.00589 AC: 355 AN: 60244

GnomAD4 genome AF: 0.00385 AC: 586 AN: 152224 Hom.: 2 Cov.: 33 AF XY: 0.00339 AC XY: 252 AN XY: 74436

African (AFR) AF: 0.00104 AC: 43 AN: 41544

American (AMR) AF: 0.00412 AC: 63 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68010

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00486 Hom.: 0

Bravo AF: 0.00407

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00622

EpiControl AF: 0.00658

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.55
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.050		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: rs41290186; hg19: chr10-94835575;