11-71444107-A-G

Variant names:

• chr11-71444107-A-G
• rs1790334
• NM_001360.3:c.207T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360.3(DHCR7):​c.207T>C​(p.Thr69Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 1,612,316 control chromosomes in the GnomAD database, including 693,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T69T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.90 (61539 hom., cov: 33)
  • Exomes 𝑓: 0.93 (631854 hom.)
• Consequence: DHCR7 NM_001360.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -3.42
• Publications: 31 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-71444107-A-G is Benign according to our data. Variant chr11-71444107-A-G is described in ClinVar as Benign. ClinVar VariationId is 93715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360.3. 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.207T>C	p.Thr69Thr	synonymous	Exon 4 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.207T>C	p.Thr69Thr	synonymous	Exon 4 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.207T>C	p.Thr69Thr	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.207T>C	p.Thr69Thr	synonymous	Exon 4 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.207T>C	p.Thr69Thr	synonymous	Exon 4 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.-333-46T>C		intron	N/A	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136326 AN: 152110 Hom.: 61508 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.896

GnomAD2 exomes AF: 0.872 AC: 215917 AN: 247586 AF XY: 0.870

Gnomad AFR exome AF: 0.837

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.850

Gnomad EAS exome AF: 0.849

Gnomad FIN exome AF: 0.946

Gnomad NFE exome AF: 0.950

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.927 AC: 1353425 AN: 1460088 Hom.: 631854 Cov.: 56 AF XY: 0.921 AC XY: 668479 AN XY: 726190

African (AFR) AF: 0.829 AC: 27729 AN: 33452

American (AMR) AF: 0.778 AC: 34484 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 22157 AN: 26112

East Asian (EAS) AF: 0.868 AC: 34393 AN: 39628

South Asian (SAS) AF: 0.688 AC: 59146 AN: 85936

European-Finnish (FIN) AF: 0.945 AC: 50287 AN: 53204

Middle Eastern (MID) AF: 0.800 AC: 4611 AN: 5764

European-Non Finnish (NFE) AF: 0.959 AC: 1066263 AN: 1111330

Other (OTH) AF: 0.901 AC: 54355 AN: 60344

GnomAD4 genome AF: 0.896 AC: 136408 AN: 152228 Hom.: 61539 Cov.: 33 AF XY: 0.892 AC XY: 66388 AN XY: 74408

African (AFR) AF: 0.839 AC: 34853 AN: 41528

American (AMR) AF: 0.845 AC: 12931 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2912 AN: 3472

East Asian (EAS) AF: 0.843 AC: 4356 AN: 5170

South Asian (SAS) AF: 0.679 AC: 3268 AN: 4816

European-Finnish (FIN) AF: 0.946 AC: 10037 AN: 10614

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65006 AN: 68016

Other (OTH) AF: 0.894 AC: 1888 AN: 2112

Alfa AF: 0.923 Hom.: 90858

Bravo AF: 0.888

Asia WGS AF: 0.706 AC: 2456 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)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.061
DANN	Benign	0.56
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1790334; hg19: chr11-71155153; COSMIC: COSV62796119; COSMIC: COSV62796119;