rs35755269
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005219.5(DIAPH1):c.3765G>A(p.Glu1255Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,614,236 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_005219.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.3765G>A | p.Glu1255Glu | synonymous_variant | Exon 28 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.3738G>A | p.Glu1246Glu | synonymous_variant | Exon 27 of 27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000468119.3 | c.171G>A | p.Glu57Glu | synonymous_variant | Exon 3 of 3 | 4 | ENSP00000493546.1 | |||
DIAPH1 | ENST00000647433 | c.*65G>A | 3_prime_UTR_variant | Exon 29 of 29 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.00883 AC: 1344AN: 152242Hom.: 26 Cov.: 33
GnomAD3 exomes AF: 0.00219 AC: 547AN: 249536Hom.: 10 AF XY: 0.00171 AC XY: 231AN XY: 135390
GnomAD4 exome AF: 0.000847 AC: 1238AN: 1461876Hom.: 17 Cov.: 30 AF XY: 0.000741 AC XY: 539AN XY: 727236
GnomAD4 genome AF: 0.00882 AC: 1344AN: 152360Hom.: 26 Cov.: 33 AF XY: 0.00847 AC XY: 631AN XY: 74500
ClinVar
Submissions by phenotype
not specified Benign:2
Glu1255Glu in Exon 28 of DIAPH1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 2.2% (79/3520) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs35755269). -
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. -
Autosomal dominant nonsyndromic hearing loss 1 Benign:1
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. -
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at