chr4-165994701-G-A

Position:

• chr4-165994701-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012464.5(TLL1):​c.514+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,142 control chromosomes in the GnomAD database, including 41,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.73 (41332 hom., cov: 33)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.645

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-165994701-G-A is Benign according to our data. Variant chr4-165994701-G-A is described in ClinVar as [Benign]. Clinvar id is 1239489.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL1	NM_012464.5	c.514+168G>A		intron_variant		ENST00000061240.7
TLL1	NM_001204760.2	c.514+168G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL1	ENST00000061240.7	c.514+168G>A		intron_variant		1	NM_012464.5	P1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111492 AN: 152024 Hom.: 41283 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.734 AC: 111606 AN: 152142 Hom.: 41332 Cov.: 33 AF XY: 0.730 AC XY: 54327 AN XY: 74382

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.738

Alfa AF: 0.722 Hom.: 25123

Bravo AF: 0.752

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.49

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: rs4691229; hg19: chr4-166915853;