4-165944433-G-T

Variant names:

• chr4-165944433-G-T
• rs7691872
• NM_012464.5:c.170-44948G>T

Variant summary

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

The NM_012464.5(TLL1):​c.170-44948G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,104 control chromosomes in the GnomAD database, including 2,534 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 0.11 (2534 hom., cov: 32)
• Consequence: TLL1 NM_012464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLL1	NM_012464.5	c.170-44948G>T		intron_variant	Intron 1 of 20	ENST00000061240.7	NP_036596.3
TLL1	NM_001204760.2	c.170-44948G>T		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.170-44948G>T		intron_variant	Intron 1 of 20	1	NM_012464.5	ENSP00000061240.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17014 AN: 151986 Hom.: 2522 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0935

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

GnomAD4 genome AF: 0.112 AC: 17060 AN: 152104 Hom.: 2534 Cov.: 32 AF XY: 0.108 AC XY: 8029 AN XY: 74360

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.0292 Hom.: 138

Bravo AF: 0.126

Asia WGS AF: 0.0410 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.56

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: rs7691872; hg19: chr4-166865585;