rs1503292

Positions:

• chr4-165946723-A-C

Variant summary

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

The NM_012464.5(TLL1):​c.170-42658A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,070 control chromosomes in the GnomAD database, including 5,042 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 0.16 (5042 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL1	NM_012464.5	c.170-42658A>C		intron_variant		ENST00000061240.7
TLL1	NM_001204760.2	c.170-42658A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL1	ENST00000061240.7	c.170-42658A>C		intron_variant		1	NM_012464.5	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23481 AN: 151952 Hom.: 5011 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0312

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.155 AC: 23572 AN: 152070 Hom.: 5042 Cov.: 32 AF XY: 0.149 AC XY: 11111 AN XY: 74350

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0365 Hom.: 1146

Bravo AF: 0.174

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.68

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: rs1503292; hg19: chr4-166867875;