9-79718839-C-T

Variant names:

• chr9-79718839-C-T
• rs61742686
• NM_007005.6:c.1458C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_007005.6(TLE4):​c.1458C>T​(p.His486His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,132 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (12 hom.)
• Consequence: TLE4 NM_007005.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100
• Publications: 2 publications found

Genes affected

TLE4 (HGNC:11840): (TLE family member 4, transcriptional corepressor) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant 9-79718839-C-T is Benign according to our data. Variant chr9-79718839-C-T is described in ClinVar as Benign. ClinVar VariationId is 786909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.001 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00759 (1156/152244) while in subpopulation AFR AF = 0.0265 (1099/41532). AF 95% confidence interval is 0.0252. There are 15 homozygotes in GnomAd4. There are 573 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1156 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007005.6. 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
	TLE4	NM_007005.6	MANE Select	c.1458C>T	p.His486His	synonymous	Exon 15 of 20	NP_008936.2
	TLE4	NM_001282748.2		c.1554C>T	p.His518His	synonymous	Exon 16 of 21	NP_001269677.1	Q04727-3
	TLE4	NM_001351541.2		c.1497C>T	p.His499His	synonymous	Exon 16 of 21	NP_001338470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE4	ENST00000376552.8	TSL:1 MANE Select	c.1458C>T	p.His486His	synonymous	Exon 15 of 20	ENSP00000365735.2	Q04727-1
	TLE4	ENST00000376537.8	TSL:1	c.1554C>T	p.His518His	synonymous	Exon 16 of 21	ENSP00000365720.4	Q04727-3
	TLE4	ENST00000376544.7	TSL:1	c.1251C>T	p.His417His	synonymous	Exon 13 of 18	ENSP00000365727.4	Q04727-2

Frequencies

GnomAD3 genomes AF: 0.00760 AC: 1156 AN: 152126 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00195 AC: 491 AN: 251484 AF XY: 0.00148

Gnomad AFR exome AF: 0.0270

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000738 AC: 1079 AN: 1461888 Hom.: 12 Cov.: 31 AF XY: 0.000683 AC XY: 497 AN XY: 727244

African (AFR) AF: 0.0268 AC: 897 AN: 33480

American (AMR) AF: 0.00110 AC: 49 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112006

Other (OTH) AF: 0.00144 AC: 87 AN: 60396

GnomAD4 genome AF: 0.00759 AC: 1156 AN: 152244 Hom.: 15 Cov.: 32 AF XY: 0.00770 AC XY: 573 AN XY: 74432

African (AFR) AF: 0.0265 AC: 1099 AN: 41532

American (AMR) AF: 0.00288 AC: 44 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00422 Hom.: 4

Bravo AF: 0.00872

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.6
DANN	Benign	0.76
PhyloP100		0.0010
Mutation Taster		=89/11	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: rs61742686; hg19: chr9-82333754;