rs189993760
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024915.4(GRHL2):c.1098+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,549,974 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0054 ( 25 hom. )
Consequence
GRHL2
NM_024915.4 intron
NM_024915.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.535
Genes affected
GRHL2 (HGNC:2799): (grainyhead like transcription factor 2) The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 8-101599160-C-T is Benign according to our data. Variant chr8-101599160-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 46214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-101599160-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00365 (556/152272) while in subpopulation NFE AF= 0.00648 (441/68020). AF 95% confidence interval is 0.00598. There are 1 homozygotes in gnomad4. There are 243 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL2 | NM_024915.4 | c.1098+9C>T | intron_variant | ENST00000646743.1 | |||
GRHL2 | NM_001330593.2 | c.1050+9C>T | intron_variant | ||||
GRHL2 | XM_011517306.4 | c.1050+9C>T | intron_variant | ||||
GRHL2 | XM_011517307.4 | c.1098+9C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL2 | ENST00000646743.1 | c.1098+9C>T | intron_variant | NM_024915.4 | P1 | ||||
GRHL2 | ENST00000395927.1 | c.1050+9C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00365 AC: 556AN: 152154Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.00331 AC: 831AN: 250756Hom.: 5 AF XY: 0.00341 AC XY: 462AN XY: 135522
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GnomAD4 exome AF: 0.00539 AC: 7537AN: 1397702Hom.: 25 Cov.: 23 AF XY: 0.00516 AC XY: 3607AN XY: 699144
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 04, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 1098+9C>T in Intron 08 of GRHL2: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 0.6% (45/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2018 | 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. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | GRHL2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Autosomal dominant nonsyndromic hearing loss 28;C4014987:Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome;C4747961:Corneal dystrophy, posterior polymorphous, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 15, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at