rs7973381

Variant names:

• chr12-57466263-C-T
• rs7973381
• NM_005269.3:c.786C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57466263-C-T
• chr12-57466263-C-A
• chr12-57466263-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005269.3(GLI1):​c.786C>T​(p.His262His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,368 control chromosomes in the GnomAD database, including 1,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.056 (491 hom., cov: 32)
  • Exomes 𝑓: 0.023 (817 hom.)
• Consequence: GLI1 NM_005269.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.84
• Publications: 20 publications found

Genes affected

GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

GLI1 Gene-Disease associations (from GenCC):

• Ellis-van Creveld syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly of a biphalangeal thumb

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type A8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 12-57466263-C-T is Benign according to our data. Variant chr12-57466263-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056398.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005269.3. 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
	GLI1	NM_005269.3	MANE Select	c.786C>T	p.His262His	synonymous	Exon 8 of 12	NP_005260.1	P08151-1
	GLI1	NM_001167609.2		c.663C>T	p.His221His	synonymous	Exon 7 of 11	NP_001161081.1	P08151-2
	GLI1	NM_001160045.2		c.402C>T	p.His134His	synonymous	Exon 6 of 10	NP_001153517.1	P08151-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI1	ENST00000228682.7	TSL:1 MANE Select	c.786C>T	p.His262His	synonymous	Exon 8 of 12	ENSP00000228682.2	P08151-1
	GLI1	ENST00000528467.1	TSL:1	c.663C>T	p.His221His	synonymous	Exon 6 of 10	ENSP00000434408.1	P08151-2
	GLI1	ENST00000546141.5	TSL:5	c.663C>T	p.His221His	synonymous	Exon 7 of 11	ENSP00000441006.1	P08151-2

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8565 AN: 152052 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0574

GnomAD2 exomes AF: 0.0322 AC: 8062 AN: 250590 AF XY: 0.0316

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.0223

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0184

Gnomad OTH exome AF: 0.0326

GnomAD4 exome AF: 0.0227 AC: 33231 AN: 1461198 Hom.: 817 Cov.: 32 AF XY: 0.0234 AC XY: 17037 AN XY: 726900

African (AFR) AF: 0.148 AC: 4964 AN: 33434

American (AMR) AF: 0.0238 AC: 1061 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 1240 AN: 26068

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.0481 AC: 4146 AN: 86178

European-Finnish (FIN) AF: 0.0261 AC: 1392 AN: 53404

Middle Eastern (MID) AF: 0.0609 AC: 351 AN: 5768

European-Non Finnish (NFE) AF: 0.0163 AC: 18158 AN: 1111642

Other (OTH) AF: 0.0317 AC: 1916 AN: 60356

GnomAD4 genome AF: 0.0564 AC: 8582 AN: 152170 Hom.: 491 Cov.: 32 AF XY: 0.0566 AC XY: 4207 AN XY: 74376

African (AFR) AF: 0.144 AC: 5986 AN: 41490

American (AMR) AF: 0.0332 AC: 508 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4816

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10592

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1187 AN: 68010

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0292 Hom.: 625

Bravo AF: 0.0622

Asia WGS AF: 0.0250 AC: 88 AN: 3478

EpiCase AF: 0.0218

EpiControl AF: 0.0224

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GLI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.46
DANN	Benign	0.46
PhyloP100		-1.8
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: rs7973381; hg19: chr12-57860046; COSMIC: COSV57359402; COSMIC: COSV57359402;