chr2-47059620-A-C

Position:

• chr2-47059620-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.2153-1149A>C		intron_variant		ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.2153-1149A>C		intron_variant		2	NM_020458.4	ENSP00000316699	P1

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.739

Alfa AF: 0.771 Hom.: 22356

Bravo AF: 0.707

Asia WGS AF: 0.852 AC: 2963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.51

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: rs13393256; hg19: chr2-47286759;