chr11-71434810-C-T

Variant names:

• chr11-71434810-C-T
• rs79320071
• NM_001360.3:c.*565G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001360.3(DHCR7):​c.*565G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 313,106 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: DHCR7 NM_001360.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.22
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-71434810-C-T is Benign according to our data. Variant chr11-71434810-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 882744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1823/152196) while in subpopulation AFR AF = 0.042 (1744/41520). AF 95% confidence interval is 0.0404. There are 38 homozygotes in GnomAd4. There are 834 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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.*565G>A		3_prime_UTR	Exon 9 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.*565G>A		3_prime_UTR	Exon 10 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.*565G>A		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.*565G>A		3_prime_UTR	Exon 9 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.*565G>A		3_prime_UTR	Exon 9 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.*565G>A		3_prime_UTR	Exon 8 of 8	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1825 AN: 152078 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00122 AC: 197 AN: 160910 Hom.: 6 Cov.: 0 AF XY: 0.00102 AC XY: 90 AN XY: 88010

African (AFR) AF: 0.0341 AC: 143 AN: 4188

American (AMR) AF: 0.00170 AC: 12 AN: 7044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3586

East Asian (EAS) AF: 0.00 AC: 0 AN: 6314

South Asian (SAS) AF: 0.000747 AC: 24 AN: 32148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7386

Middle Eastern (MID) AF: 0.00365 AC: 2 AN: 548

European-Non Finnish (NFE) AF: 0.0000870 AC: 8 AN: 91982

Other (OTH) AF: 0.00104 AC: 8 AN: 7714

GnomAD4 genome AF: 0.0120 AC: 1823 AN: 152196 Hom.: 38 Cov.: 32 AF XY: 0.0112 AC XY: 834 AN XY: 74412

African (AFR) AF: 0.0420 AC: 1744 AN: 41520

American (AMR) AF: 0.00314 AC: 48 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68012

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00768 Hom.: 5

Bravo AF: 0.0136

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Smith-Lemli-Opitz syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.61
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs79320071; hg19: chr11-71145856;