rs142083150
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024915.4(GRHL2):c.1517+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,612,324 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 8 hom. )
Consequence
GRHL2
NM_024915.4 intron
NM_024915.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.03
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=-0.88).
BP6
?
Variant 8-101636940-A-G is Benign according to our data. Variant chr8-101636940-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 163649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0042 (640/152202) while in subpopulation AFR AF= 0.0144 (596/41532). AF 95% confidence interval is 0.0134. There are 5 homozygotes in gnomad4. There are 299 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL2 | NM_024915.4 | c.1517+12A>G | intron_variant | ENST00000646743.1 | |||
GRHL2 | NM_001330593.2 | c.1469+12A>G | intron_variant | ||||
GRHL2 | XM_011517306.4 | c.1469+12A>G | intron_variant | ||||
GRHL2 | XM_011517307.4 | c.1517+12A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL2 | ENST00000646743.1 | c.1517+12A>G | intron_variant | NM_024915.4 | P1 | ||||
GRHL2 | ENST00000395927.1 | c.1469+12A>G | intron_variant | 2 | |||||
GRHL2 | ENST00000474338.1 | n.159+12A>G | intron_variant, non_coding_transcript_variant | 3 | |||||
GRHL2 | ENST00000517674.5 | n.172+12A>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00419 AC: 637AN: 152084Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00121 AC: 305AN: 251236Hom.: 1 AF XY: 0.000877 AC XY: 119AN XY: 135756
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GnomAD4 exome AF: 0.000576 AC: 841AN: 1460122Hom.: 8 Cov.: 30 AF XY: 0.000483 AC XY: 351AN XY: 726514
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GnomAD4 genome ? AF: 0.00420 AC: 640AN: 152202Hom.: 5 Cov.: 32 AF XY: 0.00402 AC XY: 299AN XY: 74420
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 1517+12A>G in Intron 12 of GRHL2: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 1.4% (53/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs142083150). - |
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