rs1923696

Positions:

• chr10-96394513-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012465.4(TLL2):​c.1726+674C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,080 control chromosomes in the GnomAD database, including 7,381 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 0.30 (7381 hom., cov: 32)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

TLL2 (HGNC:11844): (tolloid like 2) This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL2	NM_012465.4	c.1726+674C>T		intron_variant		ENST00000357947.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL2	ENST00000357947.4	c.1726+674C>T		intron_variant		1	NM_012465.4	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46082 AN: 151962 Hom.: 7383 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.303 AC: 46090 AN: 152080 Hom.: 7381 Cov.: 32 AF XY: 0.299 AC XY: 22223 AN XY: 74354

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.315

Alfa AF: 0.340 Hom.: 1102

Bravo AF: 0.300

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1923696; hg19: chr10-98154270;