rs149021782

Positions:

• chr22-37765832-G-GA
• chr22-37765832-G-GC
• chr22-37765832-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001039141.3(TRIOBP):​c.6472+15_6472+16insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000467 in 1,585,340 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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 -10 ACMG points.

• BP6: Variant 22-37765832-G-GA is Benign according to our data. Variant chr22-37765832-G-GA is described in ClinVar as [Benign]. Clinvar id is 1651191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000938 (142/151322) while in subpopulation EAS AF= 0.00992 (51/5142). AF 95% confidence interval is 0.00775. There are 0 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.6472+15_6472+16insA		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.1333+15_1333+16insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+15_6472+16insA		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000403663.6	c.1333+15_1333+16insA		intron_variant		1		P2
TRIOBP	ENST00000344404.10	c.*5955+15_*5955+16insA		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000939 AC: 142 AN: 151204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00990

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00702

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00121 AC: 244 AN: 202474 Hom.: 3 AF XY: 0.00110 AC XY: 123 AN XY: 111982

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0102

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000417 AC: 598 AN: 1434018 Hom.: 2 Cov.: 35 AF XY: 0.000427 AC XY: 304 AN XY: 711672

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000706

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00653

Gnomad4 SAS exome AF: 0.0000240

Gnomad4 FIN exome AF: 0.00504

Gnomad4 NFE exome AF: 0.0000662

Gnomad4 OTH exome AF: 0.000724

GnomAD4 genome AF: 0.000938 AC: 142 AN: 151322 Hom.: 0 Cov.: 32 AF XY: 0.00128 AC XY: 95 AN XY: 73964

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00992

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00702

Gnomad4 NFE AF: 0.000222

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000440 Hom.: 1

Bravo AF: 0.000400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149021782; hg19: chr22-38161839;