rs909217

Variant names:

• chr11-71435531-G-A
• rs909217
• NM_001360.3:c.1272C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-71435531-G-A
• chr11-71435531-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001360.3(DHCR7):​c.1272C>T​(p.Gly424Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,610,536 control chromosomes in the GnomAD database, including 390,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (26082 hom., cov: 35)
  • Exomes 𝑓: 0.69 (364170 hom.)
• Consequence: DHCR7 NM_001360.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.755
• Publications: 26 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 11-71435531-G-A is Benign according to our data. Variant chr11-71435531-G-A is described in ClinVar as Benign. ClinVar VariationId is 93708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.755 with no splicing effect.
• 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_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.1272C>T	p.Gly424Gly	synonymous	Exon 9 of 9	NP_001351.2	A0A024R5F7
	DHCR7	NM_001425107.1		c.1323C>T	p.Gly441Gly	synonymous	Exon 10 of 10	NP_001412036.1	A0A804HI25
	DHCR7	NM_001425108.1		c.1308C>T	p.Gly436Gly	synonymous	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.1272C>T	p.Gly424Gly	synonymous	Exon 9 of 9	ENSP00000347717.4	Q9UBM7
	DHCR7	ENST00000407721.6	TSL:1	c.1272C>T	p.Gly424Gly	synonymous	Exon 9 of 9	ENSP00000384739.2	Q9UBM7
	DHCR7	ENST00000685320.1		c.687C>T	p.Gly229Gly	synonymous	Exon 8 of 8	ENSP00000509319.1	B4E1K5

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83967 AN: 152056 Hom.: 26078 Cov.: 35

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.536

GnomAD2 exomes AF: 0.560 AC: 137399 AN: 245264 AF XY: 0.554

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.686 AC: 1001000 AN: 1458362 Hom.: 364170 Cov.: 83 AF XY: 0.673 AC XY: 488301 AN XY: 725648

African (AFR) AF: 0.293 AC: 9823 AN: 33474

American (AMR) AF: 0.528 AC: 23582 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 16355 AN: 26112

East Asian (EAS) AF: 0.349 AC: 13863 AN: 39682

South Asian (SAS) AF: 0.220 AC: 19012 AN: 86250

European-Finnish (FIN) AF: 0.589 AC: 29688 AN: 50374

Middle Eastern (MID) AF: 0.465 AC: 2680 AN: 5766

European-Non Finnish (NFE) AF: 0.763 AC: 848007 AN: 1111736

Other (OTH) AF: 0.630 AC: 37990 AN: 60310

GnomAD4 genome AF: 0.552 AC: 83991 AN: 152174 Hom.: 26082 Cov.: 35 AF XY: 0.537 AC XY: 39934 AN XY: 74408

African (AFR) AF: 0.313 AC: 13008 AN: 41512

American (AMR) AF: 0.518 AC: 7924 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1988 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4828

European-Finnish (FIN) AF: 0.569 AC: 6038 AN: 10616

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50005 AN: 67974

Other (OTH) AF: 0.530 AC: 1121 AN: 2114

Alfa AF: 0.676 Hom.: 20060

Bravo AF: 0.547

Asia WGS AF: 0.277 AC: 967 AN: 3478

EpiCase AF: 0.740

EpiControl AF: 0.737

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Smith-Lemli-Opitz syndrome (6)
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	DHCR7-related disorder (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.59
DANN	Benign	0.74
PhyloP100		-0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs909217; hg19: chr11-71146577; COSMIC: COSV62794705; COSMIC: COSV62794705;