dbSNP rs149021782: TRIOBP:c.6472+15_6472+16insA (chr22-37765832-G-GA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07

Publications

1 publications found

Variant links:

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

TRIOBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.6472+15_6472+16insA		intron_variant	Intron 18 of 23	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.1333+15_1333+16insA		intron_variant	Intron 8 of 13		NP_008963.3	Q9H2D6-7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000644935.1 link	c.6472+15_6472+16insA	intron_variant	Intron 18 of 23		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000403663.6 link	c.1333+15_1333+16insA	intron_variant	Intron 8 of 13	1		ENSP00000386026.2	Q9H2D6-7
TRIOBP	ENST00000344404.10 link	n.5955+15_5955+16insA	intron_variant	Intron 16 of 21	2		ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.000939

AC:

142

AN:

151204

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00121

AC:

244

AN:

202474

AF XY:

0.00110

show subpopulations

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 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.:

Cov.:

AF XY:

0.000427

AC XY:

304

AN XY:

711672

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33100

American (AMR)

AF:

0.0000706

AC:

AN:

42466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25708

East Asian (EAS)

AF:

0.00653

AC:

254

AN:

38892

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83382

European-Finnish (FIN)

AF:

0.00504

AC:

221

AN:

43824

Middle Eastern (MID)

AF:

0.000200

AC:

AN:

5002

European-Non Finnish (NFE)

AF:

0.0000662

AC:

AN:

1102220

Other (OTH)

AF:

0.000724

AC:

AN:

59424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000938

AC:

142

AN:

151322

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

73964

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41342

American (AMR)

AF:

0.0000656

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00992

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00702

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000222

AC:

AN:

67536

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000440

Hom.:

Bravo

AF:

0.000400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over