14-90668317-C-T

Variant names:

• chr14-90668317-C-T
• rs961196
• NM_001010854.2:c.1152+8206G>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.1152+8206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,044 control chromosomes in the GnomAD database, including 3,535 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 0.21 (3535 hom., cov: 31)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.1152+8206G>A		intron_variant	Intron 9 of 19	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.1152+8206G>A		intron_variant	Intron 9 of 21		NP_001388294.1
TTC7B	NM_001320421.2	c.846+8206G>A		intron_variant	Intron 9 of 20		NP_001307350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7B	ENST00000328459.11	c.1152+8206G>A		intron_variant	Intron 9 of 19	1	NM_001010854.2	ENSP00000336127.4
TTC7B	ENST00000554462.1	c.159+8206G>A		intron_variant	Intron 2 of 5	5		ENSP00000451928.1
TTC7B	ENST00000555005.5	n.375+8206G>A		intron_variant	Intron 3 of 14	2		ENSP00000451825.1
TTC7B	ENST00000555239.5	n.192+8206G>A		intron_variant	Intron 2 of 5	3		ENSP00000450520.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32043 AN: 151922 Hom.: 3521 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.211 AC: 32083 AN: 152044 Hom.: 3535 Cov.: 31 AF XY: 0.215 AC XY: 15950 AN XY: 74326

African (AFR) AF: 0.201 AC: 8350 AN: 41478

American (AMR) AF: 0.295 AC: 4508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1421 AN: 5166

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2085 AN: 10564

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13267 AN: 67946

Other (OTH) AF: 0.206 AC: 436 AN: 2116

Alfa AF: 0.202 Hom.: 1867

Bravo AF: 0.218

Asia WGS AF: 0.223 AC: 772 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	3.8
DANN	Benign	0.75
PhyloP100		-0.48
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: rs961196; hg19: chr14-91134661;