NM_001010854.2:c.2107+5758G>A

Variant names:

• chr14-90587728-C-T
• rs1286474
• NM_001010854.2:c.2107+5758G>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.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
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010854.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	NM_001010854.2	MANE Select	c.2107+5758G>A		intron	N/A	NP_001010854.1
	TTC7B	NM_001401365.1		c.2320+5758G>A		intron	N/A	NP_001388294.1
	TTC7B	NM_001320421.2		c.1852+5758G>A		intron	N/A	NP_001307350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.2107+5758G>A		intron	N/A	ENSP00000336127.4
	TTC7B	ENST00000553972.5	TSL:1	c.568+5758G>A		intron	N/A	ENSP00000451440.1
	TTC7B	ENST00000557292.1	TSL:3	c.388+5758G>A		intron	N/A	ENSP00000452031.1

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

African (AFR) AF: 0.0456 AC: 1895 AN: 41544

American (AMR) AF: 0.0448 AC: 685 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 330 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1094 AN: 5176

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4820

European-Finnish (FIN) AF: 0.0466 AC: 494 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4678 AN: 68016

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0648 Hom.: 661

Bravo AF: 0.0632

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.74
PhyloP100		-0.54
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: rs1286474; hg19: chr14-91054072;