11-71444125-C-T

Variant names:

• chr11-71444125-C-T
• rs1044482
• NM_001360.3:c.189G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001425113.1(DHCR7):​c.99-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,610,010 control chromosomes in the GnomAD database, including 392,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27496 hom., cov: 33)
  • Exomes 𝑓: 0.69 (364882 hom.)
• Consequence: DHCR7 NM_001425113.1 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 3.07
• Publications: 29 publications found

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]

DHCR7 Gene-Disease associations (from GenCC):

• Smith-Lemli-Opitz syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, ClinGen, Orphanet, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 11-71444125-C-T is Benign according to our data. Variant chr11-71444125-C-T is described in ClinVar as Benign. ClinVar VariationId is 93713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425113.1. 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
	DHCR7	NM_001360.3	MANE Select	c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 9	NP_001412037.1	A0A804HJQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHCR7	ENST00000355527.8	TSL:1 MANE Select	c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.-333-64G>A		intron	N/A	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87821 AN: 151986 Hom.: 27466 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.565 AC: 137936 AN: 243970 AF XY: 0.558

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.688 AC: 1002927 AN: 1457908 Hom.: 364882 Cov.: 53 AF XY: 0.674 AC XY: 488636 AN XY: 724926

African (AFR) AF: 0.373 AC: 12489 AN: 33438

American (AMR) AF: 0.539 AC: 23709 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 16335 AN: 26076

East Asian (EAS) AF: 0.333 AC: 13174 AN: 39572

South Asian (SAS) AF: 0.215 AC: 18444 AN: 85718

European-Finnish (FIN) AF: 0.587 AC: 31052 AN: 52894

Middle Eastern (MID) AF: 0.466 AC: 2684 AN: 5764

European-Non Finnish (NFE) AF: 0.763 AC: 846811 AN: 1110252

Other (OTH) AF: 0.635 AC: 38229 AN: 60230

GnomAD4 genome AF: 0.578 AC: 87896 AN: 152102 Hom.: 27496 Cov.: 33 AF XY: 0.562 AC XY: 41785 AN XY: 74340

African (AFR) AF: 0.404 AC: 16751 AN: 41472

American (AMR) AF: 0.536 AC: 8199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2137 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1893 AN: 5182

South Asian (SAS) AF: 0.203 AC: 977 AN: 4814

European-Finnish (FIN) AF: 0.569 AC: 6027 AN: 10590

Middle Eastern (MID) AF: 0.476 AC: 138 AN: 290

European-Non Finnish (NFE) AF: 0.736 AC: 50006 AN: 67978

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.665 Hom.: 19070

Bravo AF: 0.578

Asia WGS AF: 0.265 AC: 925 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Smith-Lemli-Opitz syndrome (6)
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		3.1
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1044482; hg19: chr11-71155171; COSMIC: COSV62794719; COSMIC: COSV62794719;