rs17689952

Positions:

• chr4-166018002-A-G
• chr4-166018002-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.1042+3442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 148,928 control chromosomes in the GnomAD database, including 3,131 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 0.20 (3131 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLL1	NM_012464.5	c.1042+3442A>G		intron_variant		ENST00000061240.7	NP_036596.3
TLL1	NM_001204760.2	c.1042+3442A>G		intron_variant			NP_001191689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLL1	ENST00000061240.7	c.1042+3442A>G		intron_variant		1	NM_012464.5	ENSP00000061240.2
TLL1	ENST00000507499.5	c.1042+3442A>G		intron_variant		1		ENSP00000426082.1
TLL1	ENST00000513213.5	c.1042+3442A>G		intron_variant		1		ENSP00000422937.1
TLL1	ENST00000509505.5	n.*687+3442A>G		intron_variant		1		ENSP00000422692.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29150 AN: 148810 Hom.: 3127 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.196 AC: 29164 AN: 148928 Hom.: 3131 Cov.: 32 AF XY: 0.198 AC XY: 14423 AN XY: 72822

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.205

Alfa AF: 0.221 Hom.: 6369

Bravo AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.44

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: rs17689952; hg19: chr4-166939154;