chr2-47046305-G-C

Variant names:

• chr2-47046305-G-C
• rs111758559
• NM_020458.4:c.1803-10G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020458.4(TTC7A):​c.1803-10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TTC7A NM_020458.4 intron
• Scores: Splicing: ADA: 0.00004920
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-47046305-G-C is Benign according to our data. Variant chr2-47046305-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1082772.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1803-10G>C		intron	N/A	NP_065191.2	Q9ULT0-1
	TTC7A	NM_001288951.2		c.1803-10G>C		intron	N/A	NP_001275880.1	Q9ULT0-4
	TTC7A	NM_001288953.2		c.1701-10G>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.1803-10G>C		intron	N/A	ENSP00000316699.5	Q9ULT0-1
	TTC7A	ENST00000394850.6	TSL:1	c.1803-10G>C		intron	N/A	ENSP00000378320.2	Q9ULT0-4
	TTC7A	ENST00000409825.5	TSL:1	n.*1552-10G>C		intron	N/A	ENSP00000386521.1	H0Y3V7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250832 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459254 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726066

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110192

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Multiple gastrointestinal atresias (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.67
DANN	Benign	0.72
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.0
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: rs111758559; hg19: chr2-47273444;