2-47002700-G-C

Variant names:

• chr2-47002700-G-C
• rs17540621
• NM_020458.4:c.1066-3222G>C

Variant summary

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

The NM_020458.4(TTC7A):​c.1066-3222G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,162 control chromosomes in the GnomAD database, including 153 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 0.040 (153 hom., cov: 32)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0566 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.1066-3222G>C		intron	N/A	NP_065191.2
	TTC7A	NM_001288951.2		c.1066-3222G>C		intron	N/A	NP_001275880.1
	TTC7A	NM_001288953.2		c.964-3222G>C		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.1066-3222G>C		intron	N/A	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.1066-3222G>C		intron	N/A	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*815-3222G>C		intron	N/A	ENSP00000386521.1

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6034 AN: 152044 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0397 AC: 6048 AN: 152162 Hom.: 153 Cov.: 32 AF XY: 0.0380 AC XY: 2830 AN XY: 74376

African (AFR) AF: 0.0172 AC: 713 AN: 41518

American (AMR) AF: 0.0367 AC: 562 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 176 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4816

European-Finnish (FIN) AF: 0.0438 AC: 464 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0581 AC: 3948 AN: 67982

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0467 Hom.: 33

Bravo AF: 0.0392

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.67
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

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: rs17540621; hg19: chr2-47229839;