rs140166160

Positions:

• chr2-47060786-C-A
• chr2-47060786-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020458.4(TTC7A):​c.2170C>A​(p.Gln724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,609,952 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (52 hom.)
• Consequence: TTC7A NM_020458.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.22

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004559338).
• BP6: Variant 2-47060786-C-A is Benign according to our data. Variant chr2-47060786-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 528469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47060786-C-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0045 (686/152336) while in subpopulation NFE AF= 0.00723 (492/68026). AF 95% confidence interval is 0.0067. There are 4 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.2170C>A	p.Gln724Lys	missense_variant	19/20	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.2170C>A	p.Gln724Lys	missense_variant	19/20	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152218 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00499 AC: 1246 AN: 249682 Hom.: 8 AF XY: 0.00549 AC XY: 740 AN XY: 134822

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00381

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00661

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00733

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00713 AC: 10396 AN: 1457616 Hom.: 52 Cov.: 31 AF XY: 0.00706 AC XY: 5111 AN XY: 724414

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.00166

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00687

Gnomad4 FIN exome AF: 0.000919

Gnomad4 NFE exome AF: 0.00821

Gnomad4 OTH exome AF: 0.00653

GnomAD4 genome AF: 0.00450 AC: 686 AN: 152336 Hom.: 4 Cov.: 32 AF XY: 0.00458 AC XY: 341 AN XY: 74494

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00723

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00639 Hom.: 5

Bravo AF: 0.00457

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00482 AC: 585

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00709

EpiControl AF: 0.00706

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	TTC7A: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Multiple gastrointestinal atresias Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.069	.;T;.
Eigen	Benign	0.039
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.12	B;B;.
Vest4		0.26
MVP		0.81
MPC		0.078
ClinPred		0.0082	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.40

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: rs140166160; hg19: chr2-47287925; COSMIC: COSV99766319; COSMIC: COSV99766319;