chr14-90716983-C-T

Variant names:

• chr14-90716983-C-T
• rs1749718
• NM_001010854.2:c.698+13092G>A

Variant summary

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

The NM_001010854.2(TTC7B):​c.698+13092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,864 control chromosomes in the GnomAD database, including 19,042 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 0.49 (19042 hom., cov: 31)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.698+13092G>A		intron_variant	Intron 5 of 19	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.698+13092G>A		intron_variant	Intron 5 of 21		NP_001388294.1
TTC7B	NM_001320421.2	c.392+13092G>A		intron_variant	Intron 5 of 20		NP_001307350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7B	ENST00000328459.11	c.698+13092G>A		intron_variant	Intron 5 of 19	1	NM_001010854.2	ENSP00000336127.4
TTC7B	ENST00000557766.1	c.392+13092G>A		intron_variant	Intron 4 of 6	3		ENSP00000451238.1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74445 AN: 151746 Hom.: 19002 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.491 AC: 74551 AN: 151864 Hom.: 19042 Cov.: 31 AF XY: 0.488 AC XY: 36215 AN XY: 74196

African (AFR) AF: 0.587 AC: 24312 AN: 41438

American (AMR) AF: 0.493 AC: 7516 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3468

East Asian (EAS) AF: 0.0933 AC: 481 AN: 5158

South Asian (SAS) AF: 0.372 AC: 1790 AN: 4806

European-Finnish (FIN) AF: 0.467 AC: 4923 AN: 10536

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32522 AN: 67914

Other (OTH) AF: 0.481 AC: 1009 AN: 2098

Alfa AF: 0.474 Hom.: 72170

Bravo AF: 0.496

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.35
PhyloP100		-1.4
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: rs1749718; hg19: chr14-91183327;