2-218741495-T-G

Position:

• chr2-218741495-T-G

Variant summary

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

The ENST00000392102.6(TTLL4):​c.1661+911T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,026 control chromosomes in the GnomAD database, including 23,168 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 0.53 (23168 hom., cov: 32)
• Consequence: TTLL4 ENST00000392102.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

Genes affected

TTLL4 (HGNC:28976): (tubulin tyrosine ligase like 4) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to act upstream of or within regulation of blastocyst development. Predicted to be located in cytosol. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL4	NM_014640.5	c.1661+911T>G		intron_variant		ENST00000392102.6	NP_055455.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL4	ENST00000392102.6	c.1661+911T>G		intron_variant		1	NM_014640.5	ENSP00000375951	P1
TTLL4	ENST00000258398.8	c.1661+911T>G		intron_variant		2		ENSP00000258398	P1
TTLL4	ENST00000442769.5	c.1661+911T>G		intron_variant		5		ENSP00000396555
TTLL4	ENST00000457313.5	c.1166+911T>G		intron_variant		2		ENSP00000393332

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80951 AN: 151908 Hom.: 23132 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.533 AC: 81037 AN: 152026 Hom.: 23168 Cov.: 32 AF XY: 0.526 AC XY: 39140 AN XY: 74340

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.507

Alfa AF: 0.455 Hom.: 9220

Bravo AF: 0.540

Asia WGS AF: 0.290 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.8
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1554622; hg19: chr2-219606218;