rs1286474

Positions:

• chr14-90587728-C-T

Variant summary

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

The NM_001010854.2(TTC7B):​c.2107+5758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,242 control chromosomes in the GnomAD database, including 363 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 0.063 (363 hom., cov: 33)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

TTC7B (HGNC:19858): (tetratricopeptide repeat domain 7B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in cytosol and plasma membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.2107+5758G>A		intron_variant		ENST00000328459.11	NP_001010854.1
TTC7B	NM_001320421.2	c.1852+5758G>A		intron_variant			NP_001307350.1
TTC7B	NM_001401365.1	c.2320+5758G>A		intron_variant			NP_001388294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7B	ENST00000328459.11	c.2107+5758G>A		intron_variant		1	NM_001010854.2	ENSP00000336127	P1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9579 AN: 152124 Hom.: 364 Cov.: 33

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0630 AC: 9587 AN: 152242 Hom.: 363 Cov.: 33 AF XY: 0.0621 AC XY: 4623 AN XY: 74438

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0950

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0643 Hom.: 454

Bravo AF: 0.0632

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.74

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: rs1286474; hg19: chr14-91054072;