Variant 5-141584136-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005219.5(DIAPH1):c.390C>T(p.Tyr130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,607,476 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 274 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 281 hom. )

Consequence

DIAPH1
NM_005219.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DIAPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 5-141584136-G-A is Benign according to our data. Variant chr5-141584136-G-A is described in ClinVar as [Benign]. Clinvar id is 163078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIAPH1	NM_005219.5 linkuse as main transcript	c.390C>T	p.Tyr130=	synonymous_variant	4/28	ENST00000389054.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIAPH1	ENST00000389054.8 linkuse as main transcript	c.390C>T	p.Tyr130=	synonymous_variant	4/28	5	NM_005219.5	A2	O60610-1

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5210

AN:

151994

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00908

AC:

2258

AN:

248734

Hom.:

125

AF XY:

0.00645

AC XY:

870

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.00748

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00348

AC:

5062

AN:

1455378

Hom.:

281

Cov.:

AF XY:

0.00290

AC XY:

2101

AN XY:

724412

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.00846

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.00739

GnomAD4 genome

AF:

0.0343

AC:

5219

AN:

152098

Hom.:

274

Cov.:

AF XY:

0.0328

AC XY:

2440

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0391

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Tyr130Tyr in Exon 04 of DIAPH1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 11.9% (376/3154) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34296458). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal dominant nonsyndromic hearing loss 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 12, 2018

- -

Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.5

DANN

Benign

0.51

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over