2-47046372-C-T

Variant names:

• chr2-47046372-C-T
• rs13427658
• NM_020458.4:c.1860C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020458.4(TTC7A):​c.1860C>T​(p.Leu620Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,614,128 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (211 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (213 hom.)
• Consequence: TTC7A NM_020458.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.33
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 2-47046372-C-T is Benign according to our data. Variant chr2-47046372-C-T is described in ClinVar as Benign. ClinVar VariationId is 458794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0953 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.1860C>T	p.Leu620Leu	synonymous	Exon 16 of 20	NP_065191.2
	TTC7A	NM_001288951.2		c.1860C>T	p.Leu620Leu	synonymous	Exon 16 of 21	NP_001275880.1
	TTC7A	NM_001288953.2		c.1758C>T	p.Leu586Leu	synonymous	Exon 17 of 21	NP_001275882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.1860C>T	p.Leu620Leu	synonymous	Exon 16 of 20	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.1860C>T	p.Leu620Leu	synonymous	Exon 16 of 21	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.*1609C>T		non_coding_transcript_exon	Exon 17 of 21	ENSP00000386521.1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4268 AN: 152144 Hom.: 211 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00757 AC: 1904 AN: 251440 AF XY: 0.00584

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00308 AC: 4500 AN: 1461866 Hom.: 213 Cov.: 31 AF XY: 0.00270 AC XY: 1965 AN XY: 727242

African (AFR) AF: 0.105 AC: 3522 AN: 33476

American (AMR) AF: 0.00465 AC: 208 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00191 AC: 165 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000166 AC: 185 AN: 1112004

Other (OTH) AF: 0.00626 AC: 378 AN: 60394

GnomAD4 genome AF: 0.0281 AC: 4272 AN: 152262 Hom.: 211 Cov.: 33 AF XY: 0.0268 AC XY: 1994 AN XY: 74438

African (AFR) AF: 0.0978 AC: 4065 AN: 41544

American (AMR) AF: 0.00843 AC: 129 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68018

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0111 Hom.: 42

Bravo AF: 0.0322

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Multiple gastrointestinal atresias (1)
-	-	1	TTC7A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs13427658; hg19: chr2-47273511;