rs1742083

Variant names:

• chr14-90720326-G-A
• rs1742083
• NM_001010854.2:c.698+9749C>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+9749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,926 control chromosomes in the GnomAD database, including 29,819 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 0.62 (29819 hom., cov: 31)
• Consequence: TTC7B NM_001010854.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.698+9749C>T		intron_variant	Intron 5 of 19	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.698+9749C>T		intron_variant	Intron 5 of 21		NP_001388294.1
TTC7B	NM_001320421.2	c.392+9749C>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+9749C>T		intron_variant	Intron 5 of 19	1	NM_001010854.2	ENSP00000336127.4
TTC7B	ENST00000557766.1	c.392+9749C>T		intron_variant	Intron 4 of 6	3		ENSP00000451238.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94617 AN: 151808 Hom.: 29815 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.623 AC: 94653 AN: 151926 Hom.: 29819 Cov.: 31 AF XY: 0.617 AC XY: 45783 AN XY: 74224

African (AFR) AF: 0.662 AC: 27412 AN: 41404

American (AMR) AF: 0.683 AC: 10444 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2275 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2245 AN: 5164

South Asian (SAS) AF: 0.495 AC: 2385 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5602 AN: 10524

Middle Eastern (MID) AF: 0.654 AC: 191 AN: 292

European-Non Finnish (NFE) AF: 0.623 AC: 42322 AN: 67952

Other (OTH) AF: 0.626 AC: 1320 AN: 2110

Alfa AF: 0.628 Hom.: 56937

Bravo AF: 0.635

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.47
PhyloP100		-1.7
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: rs1742083; hg19: chr14-91186670;