22-37710252-A-T

Variant names:

• chr22-37710252-A-T
• rs4821691
• NM_001039141.3:c.115-175A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039141.3(TRIOBP):​c.115-175A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,230 control chromosomes in the GnomAD database, including 22,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (22802 hom., cov: 35)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419
• Publications: 8 publications found

Genes affected

TRIOBP (HGNC:17009): (TRIO and F-actin binding protein) This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]

TRIOBP Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ENSG00000100101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-37710252-A-T is Benign according to our data. Variant chr22-37710252-A-T is described in ClinVar as [Benign]. Clinvar id is 1261002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.115-175A>T		intron_variant	Intron 3 of 23	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.115-175A>T		intron_variant	Intron 3 of 23		NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*451-175A>T		intron_variant	Intron 9 of 12	5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.251-175A>T		intron_variant	Intron 2 of 4	1
TRIOBP	ENST00000344404.10	n.115-175A>T		intron_variant	Intron 2 of 21	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81948 AN: 152112 Hom.: 22798 Cov.: 35

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.545

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 81992 AN: 152230 Hom.: 22802 Cov.: 35 AF XY: 0.537 AC XY: 39936 AN XY: 74424

African (AFR) AF: 0.396 AC: 16465 AN: 41552

American (AMR) AF: 0.596 AC: 9120 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3599 AN: 5164

South Asian (SAS) AF: 0.501 AC: 2418 AN: 4830

European-Finnish (FIN) AF: 0.567 AC: 6019 AN: 10612

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 40964 AN: 67990

Other (OTH) AF: 0.548 AC: 1158 AN: 2114

Alfa AF: 0.565 Hom.: 3042

Bravo AF: 0.538

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.80
PhyloP100		0.42
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: rs4821691; hg19: chr22-38106259;