rs11704996

Variant names:

• chr22-37755163-G-A
• rs11704996
• NM_001039141.3:c.5550G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37755163-G-A
• chr22-37755163-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001039141.3(TRIOBP):​c.5550G>A​(p.Val1850Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,060 control chromosomes in the GnomAD database, including 2,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (298 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2512 hom.)
• Consequence: TRIOBP NM_001039141.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.474
• Publications: 6 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)
• hearing loss, autosomal recessive

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.068).
• BP6: Variant 22-37755163-G-A is Benign according to our data. Variant chr22-37755163-G-A is described in ClinVar as Benign. ClinVar VariationId is 43862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.474 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.5550G>A	p.Val1850Val	synonymous	Exon 14 of 24	NP_001034230.1	Q9H2D6-1
	TRIOBP	NM_007032.5		c.411G>A	p.Val137Val	synonymous	Exon 4 of 14	NP_008963.3	Q9H2D6-7
	TRIOBP	NM_138632.2		c.411G>A	p.Val137Val	synonymous	Exon 4 of 8	NP_619538.2	Q9H2D6-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.5550G>A	p.Val1850Val	synonymous	Exon 14 of 24	ENSP00000496394.1	Q9H2D6-1
	TRIOBP	ENST00000403663.6	TSL:1	c.411G>A	p.Val137Val	synonymous	Exon 4 of 14	ENSP00000386026.2	Q9H2D6-7
	TRIOBP	ENST00000407319.7	TSL:1	c.411G>A	p.Val137Val	synonymous	Exon 4 of 8	ENSP00000383913.2	Q9H2D6-6

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9104 AN: 152134 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0581 AC: 14454 AN: 248862 AF XY: 0.0542

Gnomad AFR exome AF: 0.0520

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.0454

Gnomad FIN exome AF: 0.0505

Gnomad NFE exome AF: 0.0558

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0567 AC: 82808 AN: 1460808 Hom.: 2512 Cov.: 34 AF XY: 0.0553 AC XY: 40199 AN XY: 726604

African (AFR) AF: 0.0559 AC: 1871 AN: 33450

American (AMR) AF: 0.104 AC: 4636 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 1106 AN: 26128

East Asian (EAS) AF: 0.0320 AC: 1270 AN: 39626

South Asian (SAS) AF: 0.0337 AC: 2901 AN: 86074

European-Finnish (FIN) AF: 0.0540 AC: 2880 AN: 53322

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5768

European-Non Finnish (NFE) AF: 0.0581 AC: 64594 AN: 1111546

Other (OTH) AF: 0.0568 AC: 3428 AN: 60346

GnomAD4 genome AF: 0.0598 AC: 9109 AN: 152252 Hom.: 298 Cov.: 32 AF XY: 0.0599 AC XY: 4460 AN XY: 74442

African (AFR) AF: 0.0540 AC: 2246 AN: 41558

American (AMR) AF: 0.0915 AC: 1400 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3470

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5176

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4828

European-Finnish (FIN) AF: 0.0572 AC: 606 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4116 AN: 68006

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0564 Hom.: 327

Bravo AF: 0.0599

Asia WGS AF: 0.0440 AC: 156 AN: 3478

EpiCase AF: 0.0554

EpiControl AF: 0.0488

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.0
DANN	Benign	0.86
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs11704996; hg19: chr22-38151170;