rs7573999

Variant names:

• chr2-218736669-A-G
• rs7573999
• NM_014640.5:c.-98-910A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-218736669-A-G
• chr2-218736669-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014640.5(TTLL4):​c.-98-910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,820 control chromosomes in the GnomAD database, including 19,512 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 0.50 (19512 hom., cov: 31)
• Consequence: TTLL4 NM_014640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL4	NM_014640.5	c.-98-910A>G		intron_variant	Intron 2 of 19	ENST00000392102.6	NP_055455.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL4	ENST00000392102.6	c.-98-910A>G		intron_variant	Intron 2 of 19	1	NM_014640.5	ENSP00000375951.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75425 AN: 151702 Hom.: 19482 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.497 AC: 75507 AN: 151820 Hom.: 19512 Cov.: 31 AF XY: 0.491 AC XY: 36464 AN XY: 74190

African (AFR) AF: 0.609 AC: 25214 AN: 41380

American (AMR) AF: 0.453 AC: 6903 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3470

East Asian (EAS) AF: 0.140 AC: 725 AN: 5172

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4814

European-Finnish (FIN) AF: 0.521 AC: 5483 AN: 10526

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32561 AN: 67902

Other (OTH) AF: 0.478 AC: 1009 AN: 2110

Alfa AF: 0.486 Hom.: 2813

Bravo AF: 0.500

Asia WGS AF: 0.284 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.4
DANN	Benign	0.67
PhyloP100		0.32
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: rs7573999; hg19: chr2-219601392;