rs140726085

Variant names:

• chr14-90578192-G-T
• rs140726085
• NM_001010854.2:c.2224C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-90578192-G-T
• chr14-90578192-G-A
• chr14-90578192-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001010854.2(TTC7B):​c.2224C>A​(p.Leu742Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,614,154 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (35 hom.)
• Consequence: TTC7B NM_001010854.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.10
• Publications: 8 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009799242).
• BP6: Variant 14-90578192-G-T is Benign according to our data. Variant chr14-90578192-G-T is described in ClinVar as Benign. ClinVar VariationId is 773559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.2224C>A	p.Leu742Ile	missense	Exon 19 of 20	NP_001010854.1	Q86TV6-1
	TTC7B	NM_001401365.1		c.2437C>A	p.Leu813Ile	missense	Exon 21 of 22	NP_001388294.1
	TTC7B	NM_001320421.2		c.1969C>A	p.Leu657Ile	missense	Exon 20 of 21	NP_001307350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.2224C>A	p.Leu742Ile	missense	Exon 19 of 20	ENSP00000336127.4	Q86TV6-1
	TTC7B	ENST00000553972.5	TSL:1	c.685C>A	p.Leu229Ile	missense	Exon 6 of 7	ENSP00000451440.1	A0A0C4DGK5
	TTC7B	ENST00000963264.1		c.2386C>A	p.Leu796Ile	missense	Exon 20 of 21	ENSP00000633323.1

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 649 AN: 152264 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00405 AC: 1015 AN: 250748 AF XY: 0.00405

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00222

Gnomad NFE exome AF: 0.00716

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00667 AC: 9750 AN: 1461772 Hom.: 35 Cov.: 32 AF XY: 0.00638 AC XY: 4641 AN XY: 727168

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.00103 AC: 46 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00208 AC: 179 AN: 86202

European-Finnish (FIN) AF: 0.00198 AC: 106 AN: 53404

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00819 AC: 9105 AN: 1111988

Other (OTH) AF: 0.00439 AC: 265 AN: 60390

GnomAD4 genome AF: 0.00426 AC: 649 AN: 152382 Hom.: 2 Cov.: 33 AF XY: 0.00401 AC XY: 299 AN XY: 74520

African (AFR) AF: 0.00168 AC: 70 AN: 41596

American (AMR) AF: 0.00111 AC: 17 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00616 Hom.: 7

Bravo AF: 0.00436

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00756 AC: 65

ExAC AF: 0.00400 AC: 485

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00540

EpiControl AF: 0.00617

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.21
Sift	Benign	0.31	T
Sift4G	Benign	0.39	T
Polyphen		1.0	D
Vest4		0.49
MVP		0.15
MPC		1.0
ClinPred		0.051	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.12
Mutation Taster		=61/39	polymorphism

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: rs140726085; hg19: chr14-91044536; COSMIC: COSV60632337;