Variant chr2-47005909-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020458.4(TTC7A):c.1066-13G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,518 control chromosomes in the GnomAD database, including 15,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2728 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12382 hom. )

Consequence

TTC7A
NM_020458.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.281

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-47005909-G-A is Benign according to our data. Variant chr2-47005909-G-A is described in ClinVar as [Benign]. Clinvar id is 403573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4 linkuse as main transcript	c.1066-13G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11 linkuse as main transcript	c.1066-13G>A		splice_polypyrimidine_tract_variant, intron_variant		2	NM_020458.4	ENSP00000316699	P1	Q9ULT0-1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25823

AN:

151974

Hom.:

2721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0976

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.130

AC:

32638

AN:

250978

Hom.:

2533

AF XY:

0.128

AC XY:

17303

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.000924

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.125

AC:

183011

AN:

1461426

Hom.:

12382

Cov.:

AF XY:

0.125

AC XY:

90583

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.170

AC:

25863

AN:

152092

Hom.:

2728

Cov.:

AF XY:

0.168

AC XY:

12482

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0975

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.138

Hom.:

1611

Bravo

AF:

0.177

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Multiple gastrointestinal atresias

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.4

DANN

Benign

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over