rs1346309649

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005219.5(DIAPH1):c.118-9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DIAPH1
NM_005219.5 intron

Scores

Splicing: ADA: 0.00002186

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.236

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
autosomal dominant nonsyndromic hearing loss 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

DIAPH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-141588259-C-G is Benign according to our data. Variant chr5-141588259-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1146625.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5 link	c.118-9G>C		intron_variant	Intron 1 of 27	ENST00000389054.8	NP_005210.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DIAPH1	ENST00000389054.8 link	c.118-9G>C	intron_variant	Intron 1 of 27	5	NM_005219.5	ENSP00000373706.4
DIAPH1	ENST00000518047.5 link	c.118-1062G>C	intron_variant	Intron 1 of 26	5		ENSP00000428268.2
DIAPH1	ENST00000647433.1 link	c.118-9G>C	intron_variant	Intron 1 of 28			ENSP00000494675.1
DIAPH1	ENST00000523100.5 link	n.118-9G>C	intron_variant	Intron 1 of 10	5		ENSP00000428208.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41324

American (AMR)

AF:

0.0000657

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67942

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Dec 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

0.24

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over