chr11-71434732-G-A

Variant names:

• chr11-71434732-G-A
• rs1044535
• NM_001360.3:c.*643C>T

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.*643C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 193,974 control chromosomes in the GnomAD database, including 70,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (55089 hom., cov: 31)
  • Exomes 𝑓: 0.86 (15791 hom.)
• Consequence: DHCR7 NM_001360.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49
• Publications: 10 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-71434732-G-A is Benign according to our data. Variant chr11-71434732-G-A is described in ClinVar as Benign. ClinVar VariationId is 305940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.*643C>T		3_prime_UTR	Exon 9 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.*643C>T		3_prime_UTR	Exon 10 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.*643C>T		3_prime_UTR	Exon 9 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.*643C>T		3_prime_UTR	Exon 9 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.*643C>T		3_prime_UTR	Exon 9 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.*643C>T		3_prime_UTR	Exon 8 of 8	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127870 AN: 151990 Hom.: 55091 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.857 AC: 35893 AN: 41866 Hom.: 15791 Cov.: 0 AF XY: 0.838 AC XY: 19063 AN XY: 22756

African (AFR) AF: 0.586 AC: 574 AN: 980

American (AMR) AF: 0.757 AC: 2612 AN: 3452

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 654 AN: 810

East Asian (EAS) AF: 0.777 AC: 1648 AN: 2120

South Asian (SAS) AF: 0.649 AC: 4545 AN: 6998

European-Finnish (FIN) AF: 0.935 AC: 1247 AN: 1334

Middle Eastern (MID) AF: 0.800 AC: 120 AN: 150

European-Non Finnish (NFE) AF: 0.946 AC: 22731 AN: 24028

Other (OTH) AF: 0.884 AC: 1762 AN: 1994

GnomAD4 genome AF: 0.841 AC: 127892 AN: 152108 Hom.: 55089 Cov.: 31 AF XY: 0.838 AC XY: 62286 AN XY: 74342

African (AFR) AF: 0.665 AC: 27555 AN: 41452

American (AMR) AF: 0.803 AC: 12273 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2892 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4008 AN: 5136

South Asian (SAS) AF: 0.675 AC: 3249 AN: 4816

European-Finnish (FIN) AF: 0.945 AC: 10031 AN: 10612

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64933 AN: 68014

Other (OTH) AF: 0.851 AC: 1798 AN: 2112

Alfa AF: 0.910 Hom.: 215268

Bravo AF: 0.824

Asia WGS AF: 0.650 AC: 2262 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Smith-Lemli-Opitz syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1044535; hg19: chr11-71145778;