2-47012873-G-T

Variant names:

• chr2-47012873-G-T
• rs10194115
• NM_020458.4:c.1392+1438G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020458.4(TTC7A):​c.1392+1438G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,214 control chromosomes in the GnomAD database, including 1,143 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.098 (1143 hom., cov: 33)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	NM_020458.4	MANE Select	c.1392+1438G>T		intron	N/A	NP_065191.2
	TTC7A	NM_001288951.2		c.1392+1438G>T		intron	N/A	NP_001275880.1
	TTC7A	NM_001288953.2		c.1290+1438G>T		intron	N/A	NP_001275882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.1392+1438G>T		intron	N/A	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.1392+1438G>T		intron	N/A	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*1141+1438G>T		intron	N/A	ENSP00000386521.1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14821 AN: 152096 Hom.: 1138 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0976 AC: 14855 AN: 152214 Hom.: 1143 Cov.: 33 AF XY: 0.0929 AC XY: 6915 AN XY: 74436

African (AFR) AF: 0.216 AC: 8966 AN: 41494

American (AMR) AF: 0.0575 AC: 879 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4832

European-Finnish (FIN) AF: 0.0437 AC: 464 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4017 AN: 68022

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0719 Hom.: 2113

Bravo AF: 0.106

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.88
PhyloP100		0.99
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: rs10194115; hg19: chr2-47240012;