rs1503298

chr4-166048493-T-C

Variant summary

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

The NM_012464.5(TLL1):c.1524+5074T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,010 control chromosomes in the GnomAD database, including 19,334 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 0.49 (19334 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL1	NM_012464.5	c.1524+5074T>C		intron_variant		ENST00000061240.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL1	ENST00000061240.7	c.1524+5074T>C		intron_variant		1	NM_012464.5	P1
TLL1	ENST00000507499.5	c.1593+4060T>C		intron_variant		1
TLL1	ENST00000509505.5	c.*1169+5074T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74887 AN: 151892 Hom.: 19297 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.493 AC: 74969 AN: 152010 Hom.: 19334 Cov.: 32 AF XY: 0.492 AC XY: 36562 AN XY: 74294

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.493

Alfa AF: 0.497 Hom.: 2846

Bravo AF: 0.494

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.4
Dann	Benign	0.76

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: rs1503298; hg19: chr4-166969645;