rs17172001

Variant names:

• chr7-42066037-G-A
• rs17172001
• NM_000168.6:c.473+10715C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000168.6(GLI3):​c.473+10715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 152,234 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (155 hom., cov: 32)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

Genes affected

GLI3 (HGNC:4319): (GLI family zinc finger 3) This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0356 (5412/152234) while in subpopulation NFE AF= 0.0507 (3447/68018). AF 95% confidence interval is 0.0493. There are 155 homozygotes in gnomad4. There are 2722 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI3	NM_000168.6	c.473+10715C>T		intron_variant	Intron 4 of 14	ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.473+10715C>T		intron_variant	Intron 4 of 14	5	NM_000168.6	ENSP00000379258.3

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5414 AN: 152116 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.0301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0356 AC: 5412 AN: 152234 Hom.: 155 Cov.: 32 AF XY: 0.0366 AC XY: 2722 AN XY: 74432

Gnomad4 AFR AF: 0.00922

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0256

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0461 Hom.: 90

Bravo AF: 0.0309

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.2
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs17172001; hg19: chr7-42105636;