rs61738825

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020458.4(TTC7A):c.300C>T(p.Ser100Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,613,934 control chromosomes in the GnomAD database, including 8,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 593 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7481 hom. )

Consequence

TTC7A
NM_020458.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0150

Publications

8 publications found

Variant links:

Genes affected

TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

TTC7A Gene-Disease associations (from GenCC):

gastrointestinal defects and immunodeficiency syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
multiple intestinal atresia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Ambry Genetics

TTC7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-46950478-C-T is Benign according to our data. Variant chr2-46950478-C-T is described in ClinVar as Benign. ClinVar VariationId is 284146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7A	NM_020458.4 link	c.300C>T	p.Ser100Ser	synonymous_variant	Exon 2 of 20	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11 link	c.300C>T	p.Ser100Ser	synonymous_variant	Exon 2 of 20	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes

AF:

0.0783

AC:

11906

AN:

152006

Hom.:

592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0946

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0768

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0752

GnomAD2 exomes

AF:

0.0837

AC:

21038

AN:

251452

AF XY:

0.0870

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.0475

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0882

GnomAD4 exome

AF:

0.0969

AC:

141666

AN:

1461810

Hom.:

7481

Cov.:

AF XY:

0.0976

AC XY:

70985

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0293

AC:

980

AN:

33476

American (AMR)

AF:

0.0493

AC:

2206

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0916

AC:

2395

AN:

26134

East Asian (EAS)

AF:

0.000202

AC:

AN:

39698

South Asian (SAS)

AF:

0.0885

AC:

7631

AN:

86254

European-Finnish (FIN)

AF:

0.115

AC:

6122

AN:

53414

Middle Eastern (MID)

AF:

0.0678

AC:

391

AN:

5768

European-Non Finnish (NFE)

AF:

0.105

AC:

116411

AN:

1111956

Other (OTH)

AF:

0.0914

AC:

5522

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

6843

13686

20530

27373

34216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4106

8212

12318

16424

20530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0783

AC:

11909

AN:

152124

Hom.:

593

Cov.:

AF XY:

0.0795

AC XY:

5908

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0343

AC:

1425

AN:

41510

American (AMR)

AF:

0.0624

AC:

954

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0946

AC:

328

AN:

3468

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0775

AC:

372

AN:

4802

European-Finnish (FIN)

AF:

0.123

AC:

1297

AN:

10562

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7116

AN:

68010

Other (OTH)

AF:

0.0739

AC:

156

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

563

1125

1688

2250

2813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0836

Hom.:

578

Bravo

AF:

0.0709

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 13, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Multiple gastrointestinal atresias

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.6

(source)

DANN

Benign

0.71

PhyloP100

-0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over