chr14-90714816-G-A

Variant names:

• chr14-90714816-G-A
• rs1749715
• NM_001010854.2:c.698+15259C>T

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+15259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,054 control chromosomes in the GnomAD database, including 39,860 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 0.72 (39860 hom., cov: 32)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.698+15259C>T		intron_variant	Intron 5 of 19	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.698+15259C>T		intron_variant	Intron 5 of 21		NP_001388294.1
TTC7B	NM_001320421.2	c.392+15259C>T		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+15259C>T		intron_variant	Intron 5 of 19	1	NM_001010854.2	ENSP00000336127.4
TTC7B	ENST00000557766.1	c.392+15259C>T		intron_variant	Intron 4 of 6	3		ENSP00000451238.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108607 AN: 151936 Hom.: 39797 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.715 AC: 108736 AN: 152054 Hom.: 39860 Cov.: 32 AF XY: 0.713 AC XY: 53005 AN XY: 74320

African (AFR) AF: 0.878 AC: 36427 AN: 41494

American (AMR) AF: 0.684 AC: 10452 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2648 AN: 5168

South Asian (SAS) AF: 0.689 AC: 3322 AN: 4824

European-Finnish (FIN) AF: 0.635 AC: 6700 AN: 10546

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44850 AN: 67962

Other (OTH) AF: 0.691 AC: 1453 AN: 2104

Alfa AF: 0.686 Hom.: 5593

Bravo AF: 0.723

Asia WGS AF: 0.592 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.49
DANN	Benign	0.76
PhyloP100		-1.1
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: rs1749715; hg19: chr14-91181160;