chr2-47059620-A-C

Variant names:

• chr2-47059620-A-C
• rs13393256
• NM_020458.4:c.2153-1149A>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.2153-1149A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,038 control chromosomes in the GnomAD database, including 41,183 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 0.72 (41183 hom., cov: 31)
• Consequence: TTC7A NM_020458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 4 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]

STPG4 (HGNC:26850): (sperm-tail PG-rich repeat containing 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in DNA demethylation of male pronucleus and positive regulation of DNA demethylation. Predicted to act upstream of or within C-5 methylation of cytosine. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	NM_020458.4	MANE Select	c.2153-1149A>C		intron	N/A	NP_065191.2	Q9ULT0-1
	TTC7A	NM_001288951.2		c.2225-1149A>C		intron	N/A	NP_001275880.1	Q9ULT0-4
	TTC7A	NM_001288953.2		c.2051-1149A>C		intron	N/A	NP_001275882.1	G5E9G4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.2153-1149A>C		intron	N/A	ENSP00000316699.5	Q9ULT0-1
	TTC7A	ENST00000394850.6	TSL:1	c.2225-1149A>C		intron	N/A	ENSP00000378320.2	Q9ULT0-4
	TTC7A	ENST00000409825.5	TSL:1	n.*1902-1149A>C		intron	N/A	ENSP00000386521.1	H0Y3V7

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109807 AN: 151920 Hom.: 41165 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.723 AC: 109849 AN: 152038 Hom.: 41183 Cov.: 31 AF XY: 0.731 AC XY: 54345 AN XY: 74336

African (AFR) AF: 0.509 AC: 21086 AN: 41430

American (AMR) AF: 0.800 AC: 12227 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2378 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4816 AN: 5140

South Asian (SAS) AF: 0.824 AC: 3974 AN: 4820

European-Finnish (FIN) AF: 0.874 AC: 9257 AN: 10594

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53482 AN: 67974

Other (OTH) AF: 0.739 AC: 1562 AN: 2114

Alfa AF: 0.771 Hom.: 24657

Bravo AF: 0.707

Asia WGS AF: 0.852 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-0.51
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: rs13393256; hg19: chr2-47286759;