dbSNP rs28635788: TTC7A:n.*2888T>C (chr2-47074485-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000409825.5(TTC7A):n.*2888T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 151,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TTC7A
ENST00000409825.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210

Publications

1 publications found

Variant links:

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 links:

ENSG00000273269 (HGNC:):

ENSG00000273269 links:

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]

STPG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409825.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TTC7A	NM_020458.4	MANE Select	c.*562T>C	3_prime_UTR	Exon 20 of 20	NP_065191.2
TTC7A	NM_001288951.2		c.*562T>C	3_prime_UTR	Exon 21 of 21	NP_001275880.1
TTC7A	NM_001288953.2		c.*562T>C	3_prime_UTR	Exon 21 of 21	NP_001275882.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TTC7A	ENST00000409825.5	TSL:1	n.*2888T>C	non_coding_transcript_exon	Exon 21 of 21	ENSP00000386521.1
TTC7A	ENST00000484061.5	TSL:1	n.2246T>C	non_coding_transcript_exon	Exon 12 of 12
TTC7A	ENST00000491786.5	TSL:1	n.2543T>C	non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

890

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

914

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41242

American (AMR)

AF:

0.00

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000738

AC:

AN:

67788

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000366

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

(source)

DANN

Benign

0.82

PhyloP100

-0.021

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over