rs1923694

chr10-96413689-C-G

Variant summary

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

The NM_012465.4(TLL2):c.924-373G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,096 control chromosomes in the GnomAD database, including 1,044 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 0.11 (1044 hom., cov: 32)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL2	NM_012465.4	c.924-373G>C		intron_variant		ENST00000357947.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL2	ENST00000357947.4	c.924-373G>C		intron_variant		1	NM_012465.4	P1
TLL2	ENST00000469598.1	n.1001-373G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16653 AN: 151978 Hom.: 1043 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0954

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

GnomAD4 genome AF: 0.110 AC: 16666 AN: 152096 Hom.: 1044 Cov.: 32 AF XY: 0.108 AC XY: 8055 AN XY: 74346

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.111 Hom.: 107

Bravo AF: 0.108

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.3
Dann	Benign	0.58

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: rs1923694; hg19: chr10-98173446;