rs6812849

Positions:

• chr4-165951384-C-A
• chr4-165951384-C-T

Variant summary

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

The NM_012464.5(TLL1):​c.170-37997C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,980 control chromosomes in the GnomAD database, including 4,597 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 0.15 (4597 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLL1	NM_012464.5	c.170-37997C>A		intron_variant		ENST00000061240.7	NP_036596.3
TLL1	NM_001204760.2	c.170-37997C>A		intron_variant			NP_001191689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLL1	ENST00000061240.7	c.170-37997C>A		intron_variant		1	NM_012464.5	ENSP00000061240	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22343 AN: 151862 Hom.: 4571 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.0303

Gnomad FIN AF: 0.00510

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.148 AC: 22425 AN: 151980 Hom.: 4597 Cov.: 32 AF XY: 0.142 AC XY: 10578 AN XY: 74282

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0398

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.00510

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0339 Hom.: 270

Bravo AF: 0.165

Asia WGS AF: 0.0690 AC: 240 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	1.7
DANN	Benign	0.53

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: rs6812849; hg19: chr4-166872536;