22-37701495-A-G

Variant summary

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

The NM_001039141.3(TRIOBP):c.114+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,591,310 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00079 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (69 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-37701495-A-G is Benign according to our data. Variant chr22-37701495-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1223706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000788 (120/152234) while in subpopulation EAS AF= 0.0132 (68/5170). AF 95% confidence interval is 0.0106. There are 8 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.114+16A>G		intron_variant		ENST00000644935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.114+16A>G		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000492485.5	n.250+16A>G		intron_variant, non_coding_transcript_variant		1
TRIOBP	ENST00000344404.10	c.114+16A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152116 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00145 AC: 329 AN: 226794 Hom.: 2 AF XY: 0.00188 AC XY: 230 AN XY: 122282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00307

Gnomad SAS exome AF: 0.00987

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00108

GnomAD4 exome AF: 0.00171 AC: 2461 AN: 1439076 Hom.: 69 Cov.: 26 AF XY: 0.00194 AC XY: 1389 AN XY: 715496

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.0000239

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0433

Gnomad4 SAS exome AF: 0.00847

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000638

Gnomad4 OTH exome AF: 0.000670

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152234 Hom.: 8 Cov.: 32 AF XY: 0.000940 AC XY: 70 AN XY: 74436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0132

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000384 Hom.: 0

Bravo AF: 0.000193

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 05, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.7
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs117561671; hg19: chr22-38097502;