rs149360779

Variant names:

• chr2-46978782-C-T
• rs149360779
• NM_020458.4:c.649-10C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-46978782-C-T
• chr2-46978782-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020458.4(TTC7A):​c.649-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,611,588 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (59 hom.)
• Consequence: TTC7A NM_020458.4 intron
• Scores: Splicing: ADA: 0.00001130
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0560
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-46978782-C-T is Benign according to our data. Variant chr2-46978782-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 522194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00656 (998/152220) while in subpopulation NFE AF = 0.00775 (527/68008). AF 95% confidence interval is 0.0072. There are 5 homozygotes in GnomAd4. There are 529 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.649-10C>T		intron	N/A	NP_065191.2	Q9ULT0-1
	TTC7A	NM_001288951.2		c.649-10C>T		intron	N/A	NP_001275880.1	Q9ULT0-4
	TTC7A	NM_001288953.2		c.547-10C>T		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.649-10C>T		intron	N/A	ENSP00000316699.5	Q9ULT0-1
	TTC7A	ENST00000394850.6	TSL:1	c.649-10C>T		intron	N/A	ENSP00000378320.2	Q9ULT0-4
	TTC7A	ENST00000491786.5	TSL:1	n.43C>T		non_coding_transcript_exon	Exon 1 of 16

Frequencies

GnomAD3 genomes AF: 0.00658 AC: 1001 AN: 152102 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00775

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00813 AC: 2042 AN: 251252 AF XY: 0.00792

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00506

Gnomad ASJ exome AF: 0.0440

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.00748

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.00716 AC: 10444 AN: 1459368 Hom.: 59 Cov.: 29 AF XY: 0.00706 AC XY: 5126 AN XY: 726188

African (AFR) AF: 0.00105 AC: 35 AN: 33434

American (AMR) AF: 0.00535 AC: 239 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0390 AC: 1019 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00350 AC: 302 AN: 86188

European-Finnish (FIN) AF: 0.0152 AC: 813 AN: 53356

Middle Eastern (MID) AF: 0.0236 AC: 136 AN: 5764

European-Non Finnish (NFE) AF: 0.00662 AC: 7344 AN: 1109844

Other (OTH) AF: 0.00922 AC: 556 AN: 60300

GnomAD4 genome AF: 0.00656 AC: 998 AN: 152220 Hom.: 5 Cov.: 32 AF XY: 0.00711 AC XY: 529 AN XY: 74414

African (AFR) AF: 0.00130 AC: 54 AN: 41528

American (AMR) AF: 0.00589 AC: 90 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4822

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00775 AC: 527 AN: 68008

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00736 Hom.: 3

Bravo AF: 0.00601

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Multiple gastrointestinal atresias (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.026
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: rs149360779; hg19: chr2-47205921;