rs13407983

Variant names:

• chr2-47005909-G-A
• rs13407983
• NM_020458.4:c.1066-13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020458.4(TTC7A):​c.1066-13G>A variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.281
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.1066-13G>A		intron_variant	Intron 8 of 19	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.1066-13G>A		intron_variant	Intron 8 of 19	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25823 AN: 151974 Hom.: 2721 Cov.: 32

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

GnomAD2 exomes AF: 0.130 AC: 32638 AN: 250978 AF XY: 0.128

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 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.: 32 AF XY: 0.125 AC XY: 90583 AN XY: 727004

African (AFR) AF: 0.299 AC: 10022 AN: 33466

American (AMR) AF: 0.136 AC: 6082 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3786 AN: 26132

East Asian (EAS) AF: 0.000680 AC: 27 AN: 39700

South Asian (SAS) AF: 0.101 AC: 8729 AN: 86250

European-Finnish (FIN) AF: 0.131 AC: 6960 AN: 53238

Middle Eastern (MID) AF: 0.166 AC: 959 AN: 5766

European-Non Finnish (NFE) AF: 0.125 AC: 138461 AN: 1111764

Other (OTH) AF: 0.132 AC: 7985 AN: 60388

GnomAD4 genome AF: 0.170 AC: 25863 AN: 152092 Hom.: 2728 Cov.: 32 AF XY: 0.168 AC XY: 12482 AN XY: 74364

African (AFR) AF: 0.285 AC: 11798 AN: 41464

American (AMR) AF: 0.162 AC: 2478 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 525 AN: 3464

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0975 AC: 469 AN: 4810

European-Finnish (FIN) AF: 0.129 AC: 1366 AN: 10588

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8809 AN: 67980

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.143 Hom.: 2431

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

Submissions by phenotype

not specified Benign:2

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 -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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	-0.78
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		0.28
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: rs13407983; hg19: chr2-47233048;