2-47024371-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes AF: 0.139 AC: 32662 AN: 235468 Hom.: 2355 AF XY: 0.143 AC XY: 18302 AN XY: 127744

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 SAS exome AF: 0.168

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0797

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.0754

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.153

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0805

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.162

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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

Other links and lift over

dbSNP: rs11885389; hg19: chr2-47251510;