rs1503292

Variant names:

• chr4-165946723-A-C
• rs1503292
• NM_012464.5:c.170-42658A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-165946723-A-C
• chr4-165946723-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

TLL1 Gene-Disease associations (from GenCC):

• atrial septal defect 6

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Ambry Genetics
• mitral valve prolapse

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TLL1	NM_012464.5	c.170-42658A>C		intron_variant	Intron 1 of 20	ENST00000061240.7	NP_036596.3
TLL1	NM_001204760.2	c.170-42658A>C		intron_variant	Intron 1 of 9		NP_001191689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLL1	ENST00000061240.7	c.170-42658A>C		intron_variant	Intron 1 of 20	1	NM_012464.5	ENSP00000061240.2

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

African (AFR) AF: 0.486 AC: 20118 AN: 41400

American (AMR) AF: 0.0779 AC: 1190 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.0404 AC: 208 AN: 5154

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4830

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1350 AN: 68006

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.0570 Hom.: 5487

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
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1503292; hg19: chr4-166867875;