2-47024371-G-C

Variant names:

• chr2-47024371-G-C
• rs11885389
• NM_020458.4:c.1641+12G>C

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.1641+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,600,728 control chromosomes in the GnomAD database, including 18,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1996 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16817 hom.)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.497
• Publications: 3 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=-0.9).
• BP6: Variant 2-47024371-G-C is Benign according to our data. Variant chr2-47024371-G-C is described in ClinVar as Benign. ClinVar VariationId is 403574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.1641+12G>C		intron_variant	Intron 14 of 19	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.1641+12G>C		intron_variant	Intron 14 of 19	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24234 AN: 151906 Hom.: 1985 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.139 AC: 32662 AN: 235468 AF XY: 0.143

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0733

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.0773

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.150 AC: 217189 AN: 1448706 Hom.: 16817 Cov.: 32 AF XY: 0.151 AC XY: 108961 AN XY: 720240

African (AFR) AF: 0.200 AC: 6530 AN: 32700

American (AMR) AF: 0.0797 AC: 3461 AN: 43408

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4279 AN: 25754

East Asian (EAS) AF: 0.0754 AC: 2863 AN: 37946

South Asian (SAS) AF: 0.170 AC: 14367 AN: 84578

European-Finnish (FIN) AF: 0.133 AC: 7094 AN: 53152

Middle Eastern (MID) AF: 0.131 AC: 750 AN: 5730

European-Non Finnish (NFE) AF: 0.153 AC: 168684 AN: 1105590

Other (OTH) AF: 0.153 AC: 9161 AN: 59848

GnomAD4 genome AF: 0.160 AC: 24274 AN: 152022 Hom.: 1996 Cov.: 32 AF XY: 0.157 AC XY: 11673 AN XY: 74310

African (AFR) AF: 0.197 AC: 8173 AN: 41450

American (AMR) AF: 0.131 AC: 2007 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.0805 AC: 415 AN: 5154

South Asian (SAS) AF: 0.166 AC: 802 AN: 4826

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10586

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10447 AN: 67944

Other (OTH) AF: 0.162 AC: 341 AN: 2106

Alfa AF: 0.109 Hom.: 210

Bravo AF: 0.158

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

not specified Benign:1

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

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	-0.90
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-0.50
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: rs11885389; hg19: chr2-47251510;