chr22-37765832-G-GC

Position:

• chr22-37765832-G-GC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001039141.3(TRIOBP):​c.6472+15_6472+16insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,585,328 control chromosomes in the GnomAD database, including 47 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (43 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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 -16 ACMG points.

• BP6: Variant 22-37765832-G-GC is Benign according to our data. Variant chr22-37765832-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 257224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00447 (676/151322) while in subpopulation AMR AF= 0.00794 (121/15236). AF 95% confidence interval is 0.00679. There are 4 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 676 AN: 151204 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00795

Gnomad ASJ AF: 0.0151

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.000474

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00440 AC: 890 AN: 202474 Hom.: 10 AF XY: 0.00428 AC XY: 479 AN XY: 111982

Gnomad AFR exome AF: 0.00165

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00192

Gnomad FIN exome AF: 0.000736

Gnomad NFE exome AF: 0.00597

Gnomad OTH exome AF: 0.00714

GnomAD4 exome AF: 0.00611 AC: 8755 AN: 1434006 Hom.: 43 Cov.: 35 AF XY: 0.00601 AC XY: 4279 AN XY: 711668

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.00379

Gnomad4 ASJ exome AF: 0.0142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00201

Gnomad4 FIN exome AF: 0.000616

Gnomad4 NFE exome AF: 0.00690

Gnomad4 OTH exome AF: 0.00602

GnomAD4 genome AF: 0.00447 AC: 676 AN: 151322 Hom.: 4 Cov.: 32 AF XY: 0.00431 AC XY: 319 AN XY: 73964

Gnomad4 AFR AF: 0.00143

Gnomad4 AMR AF: 0.00794

Gnomad4 ASJ AF: 0.0151

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000839

Gnomad4 FIN AF: 0.000474

Gnomad4 NFE AF: 0.00622

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00319 Hom.: 1

Bravo AF: 0.00484

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2016	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	TRIOBP: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

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;