rs1630498

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001360.3(DHCR7):​c.627-656T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,072 control chromosomes in the GnomAD database, including 6,563 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 0.28 ( 6563 hom., cov: 32)

Consequence

DHCR7
NM_001360.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16
Variant links:
Genes affected
DHCR7 (HGNC:2860): (7-dehydrocholesterol reductase) This gene encodes an enzyme that removes the C(7-8) double bond in the B ring of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol. This gene is ubiquitously expressed and its transmembrane protein localizes to the endoplasmic reticulum membrane and nuclear outer membrane. Mutations in this gene cause Smith-Lemli-Opitz syndrome (SLOS); a syndrome that is metabolically characterized by reduced serum cholesterol levels and elevated serum 7-dehydrocholesterol levels and phenotypically characterized by cognitive disability, facial dysmorphism, syndactyly of second and third toes, and holoprosencephaly in severe cases to minimal physical abnormalities and near-normal intelligence in mild cases. Alternative splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Aug 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DHCR7NM_001360.3 linkuse as main transcriptc.627-656T>G intron_variant ENST00000355527.8 NP_001351.2 Q9UBM7A0A024R5F7
DHCR7NM_001163817.2 linkuse as main transcriptc.627-656T>G intron_variant NP_001157289.1 Q9UBM7A0A024R5F7
DHCR7XM_011544777.3 linkuse as main transcriptc.627-656T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHCR7ENST00000355527.8 linkuse as main transcriptc.627-656T>G intron_variant 1 NM_001360.3 ENSP00000347717.4 Q9UBM7
DHCR7ENST00000685320.1 linkuse as main transcriptc.42-656T>G intron_variant ENSP00000509319.1 B4E1K5

Frequencies

GnomAD3 genomes
AF:
0.283
AC:
43075
AN:
151954
Hom.:
6564
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.332
Gnomad AMI
AF:
0.323
Gnomad AMR
AF:
0.282
Gnomad ASJ
AF:
0.219
Gnomad EAS
AF:
0.392
Gnomad SAS
AF:
0.468
Gnomad FIN
AF:
0.377
Gnomad MID
AF:
0.365
Gnomad NFE
AF:
0.220
Gnomad OTH
AF:
0.316
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.283
AC:
43074
AN:
152072
Hom.:
6563
Cov.:
32
AF XY:
0.296
AC XY:
21973
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.331
Gnomad4 AMR
AF:
0.282
Gnomad4 ASJ
AF:
0.219
Gnomad4 EAS
AF:
0.392
Gnomad4 SAS
AF:
0.466
Gnomad4 FIN
AF:
0.377
Gnomad4 NFE
AF:
0.220
Gnomad4 OTH
AF:
0.319
Alfa
AF:
0.253
Hom.:
2426
Bravo
AF:
0.270
Asia WGS
AF:
0.370
AC:
1284
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
8.2
DANN
Benign
0.87

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: rs1630498; hg19: chr11-71150785; API