NM_001010854.2:c.1966+6298G>A

Variant names:

• chr14-90604444-C-T
• rs1014527
• NM_001010854.2:c.1966+6298G>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.1966+6298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,174 control chromosomes in the GnomAD database, including 575 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 0.080 (575 hom., cov: 33)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	NM_001010854.2	MANE Select	c.1966+6298G>A		intron	N/A	NP_001010854.1	Q86TV6-1
	TTC7B	NM_001401365.1		c.2129-1141G>A		intron	N/A	NP_001388294.1
	TTC7B	NM_001320421.2		c.1661-1141G>A		intron	N/A	NP_001307350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.1966+6298G>A		intron	N/A	ENSP00000336127.4	Q86TV6-1
	TTC7B	ENST00000553972.5	TSL:1	c.377-1141G>A		intron	N/A	ENSP00000451440.1	A0A0C4DGK5
	TTC7B	ENST00000963264.1		c.2128+1153G>A		intron	N/A	ENSP00000633323.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12131 AN: 152056 Hom.: 576 Cov.: 33

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0798 AC: 12142 AN: 152174 Hom.: 575 Cov.: 33 AF XY: 0.0783 AC XY: 5825 AN XY: 74408

African (AFR) AF: 0.0466 AC: 1934 AN: 41516

American (AMR) AF: 0.0597 AC: 912 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5176

South Asian (SAS) AF: 0.0596 AC: 287 AN: 4818

European-Finnish (FIN) AF: 0.0749 AC: 793 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6743 AN: 67994

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0889 Hom.: 1070

Bravo AF: 0.0767

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.77
PhyloP100		-0.66
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: rs1014527; hg19: chr14-91070788;