2-47020972-A-G

Variant names:

• chr2-47020972-A-G
• rs919883
• NM_020458.4:c.1393-890A>G

Variant summary

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

The NM_020458.4(TTC7A):​c.1393-890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,036 control chromosomes in the GnomAD database, including 19,559 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 0.50 (19559 hom., cov: 33)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.1393-890A>G		intron_variant	Intron 11 of 19	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.1393-890A>G		intron_variant	Intron 11 of 19	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76377 AN: 151916 Hom.: 19545 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.503 AC: 76423 AN: 152036 Hom.: 19559 Cov.: 33 AF XY: 0.505 AC XY: 37545 AN XY: 74360

African (AFR) AF: 0.413 AC: 17139 AN: 41450

American (AMR) AF: 0.556 AC: 8497 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3466

East Asian (EAS) AF: 0.568 AC: 2932 AN: 5162

South Asian (SAS) AF: 0.484 AC: 2335 AN: 4820

European-Finnish (FIN) AF: 0.584 AC: 6182 AN: 10586

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35899 AN: 67954

Other (OTH) AF: 0.514 AC: 1087 AN: 2114

Alfa AF: 0.514 Hom.: 60459

Bravo AF: 0.500

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.18
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: rs919883; hg19: chr2-47248111;