rs4485771

chr4-165972381-A-Gchr4-165972381-A-T

Variant summary

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

The NM_012464.5(TLL1):c.170-17000A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,972 control chromosomes in the GnomAD database, including 26,629 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 0.56 (26629 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

Genes affected

TLL1 (HGNC:11843): (tolloid like 1) This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL1	NM_012464.5	c.170-17000A>G		intron_variant		ENST00000061240.7
TLL1	NM_001204760.2	c.170-17000A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL1	ENST00000061240.7	c.170-17000A>G		intron_variant		1	NM_012464.5	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85662 AN: 151854 Hom.: 26621 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.564 AC: 85706 AN: 151972 Hom.: 26629 Cov.: 32 AF XY: 0.563 AC XY: 41852 AN XY: 74298

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.593

Alfa AF: 0.653 Hom.: 16370

Bravo AF: 0.564

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.43
Dann	Benign	0.51

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: rs4485771; hg19: chr4-166893533;