10-96375748-A-T

Variant names:

• chr10-96375748-A-T
• rs10786284
• NM_012465.4:c.2448+944T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012465.4(TLL2):​c.2448+944T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,730 control chromosomes in the GnomAD database, including 13,422 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 0.41 (13422 hom., cov: 31)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 21 publications found

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]

ENSG00000310117 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLL2	NM_012465.4	c.2448+944T>A		intron_variant	Intron 18 of 20	ENST00000357947.4	NP_036597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL2	ENST00000357947.4	c.2448+944T>A		intron_variant	Intron 18 of 20	1	NM_012465.4	ENSP00000350630.3
ENSG00000310117	ENST00000847278.1	n.80-810A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62551 AN: 151612 Hom.: 13401 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.413 AC: 62612 AN: 151730 Hom.: 13422 Cov.: 31 AF XY: 0.415 AC XY: 30769 AN XY: 74142

African (AFR) AF: 0.473 AC: 19545 AN: 41356

American (AMR) AF: 0.464 AC: 7090 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3462

East Asian (EAS) AF: 0.648 AC: 3334 AN: 5144

South Asian (SAS) AF: 0.435 AC: 2086 AN: 4798

European-Finnish (FIN) AF: 0.356 AC: 3750 AN: 10526

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23888 AN: 67858

Other (OTH) AF: 0.438 AC: 921 AN: 2104

Alfa AF: 0.373 Hom.: 6125

Bravo AF: 0.424

Asia WGS AF: 0.553 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		-0.17
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: rs10786284; hg19: chr10-98135505;