rs61738825

Variant names:

• chr2-46950478-C-T
• rs61738825
• NM_020458.4:c.300C>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.300C>T​(p.Ser100Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,613,934 control chromosomes in the GnomAD database, including 8,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (593 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7481 hom.)
• Consequence: TTC7A NM_020458.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0150
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-46950478-C-T is Benign according to our data. Variant chr2-46950478-C-T is described in ClinVar as Benign. ClinVar VariationId is 284146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.015 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 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.300C>T	p.Ser100Ser	synonymous	Exon 2 of 20	NP_065191.2
	TTC7A	NM_001288951.2		c.300C>T	p.Ser100Ser	synonymous	Exon 2 of 21	NP_001275880.1
	TTC7A	NM_001288953.2		c.198C>T	p.Ser66Ser	synonymous	Exon 3 of 21	NP_001275882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7A	ENST00000319190.11	TSL:2 MANE Select	c.300C>T	p.Ser100Ser	synonymous	Exon 2 of 20	ENSP00000316699.5
	TTC7A	ENST00000394850.6	TSL:1	c.300C>T	p.Ser100Ser	synonymous	Exon 2 of 21	ENSP00000378320.2
	TTC7A	ENST00000409825.5	TSL:1	n.57C>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000386521.1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11906 AN: 152006 Hom.: 592 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0752

GnomAD2 exomes AF: 0.0837 AC: 21038 AN: 251452 AF XY: 0.0870

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.0475

Gnomad ASJ exome AF: 0.0891

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0882

GnomAD4 exome AF: 0.0969 AC: 141666 AN: 1461810 Hom.: 7481 Cov.: 32 AF XY: 0.0976 AC XY: 70985 AN XY: 727220

African (AFR) AF: 0.0293 AC: 980 AN: 33476

American (AMR) AF: 0.0493 AC: 2206 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 2395 AN: 26134

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39698

South Asian (SAS) AF: 0.0885 AC: 7631 AN: 86254

European-Finnish (FIN) AF: 0.115 AC: 6122 AN: 53414

Middle Eastern (MID) AF: 0.0678 AC: 391 AN: 5768

European-Non Finnish (NFE) AF: 0.105 AC: 116411 AN: 1111956

Other (OTH) AF: 0.0914 AC: 5522 AN: 60390

GnomAD4 genome AF: 0.0783 AC: 11909 AN: 152124 Hom.: 593 Cov.: 32 AF XY: 0.0795 AC XY: 5908 AN XY: 74354

African (AFR) AF: 0.0343 AC: 1425 AN: 41510

American (AMR) AF: 0.0624 AC: 954 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 328 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0775 AC: 372 AN: 4802

European-Finnish (FIN) AF: 0.123 AC: 1297 AN: 10562

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7116 AN: 68010

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.0836 Hom.: 578

Bravo AF: 0.0709

Asia WGS AF: 0.0310 AC: 109 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.103

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Multiple gastrointestinal atresias (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		-0.015
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: rs61738825; hg19: chr2-47177617; COSMIC: COSV108020735;