8-101492313-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NR_186783.1(GRHL2-DT):​n.257-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 188,778 control chromosomes in the GnomAD database, including 88,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71128 hom., cov: 34)
Exomes 𝑓: 0.97 ( 17285 hom. )

Consequence

GRHL2-DT
NR_186783.1 splice_region, intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.184
Variant links:
Genes affected
GRHL2-DT (HGNC:55466): (GRHL2 divergent transcript)
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 8-101492313-C-T is Benign according to our data. Variant chr8-101492313-C-T is described in ClinVar as [Benign]. Clinvar id is 1222504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRHL2NM_024915.4 linkc.-457C>T upstream_gene_variant ENST00000646743.1 NP_079191.2 Q6ISB3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRHL2ENST00000646743.1 linkc.-457C>T upstream_gene_variant NM_024915.4 ENSP00000495564.1 Q6ISB3-1

Frequencies

GnomAD3 genomes
AF:
0.966
AC:
146999
AN:
152230
Hom.:
71100
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.924
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.919
Gnomad ASJ
AF:
0.999
Gnomad EAS
AF:
0.903
Gnomad SAS
AF:
0.965
Gnomad FIN
AF:
0.995
Gnomad MID
AF:
0.987
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.974
GnomAD4 exome
AF:
0.973
AC:
35459
AN:
36430
Hom.:
17285
AF XY:
0.973
AC XY:
18357
AN XY:
18874
show subpopulations
Gnomad4 AFR exome
AF:
0.924
Gnomad4 AMR exome
AF:
0.894
Gnomad4 ASJ exome
AF:
0.999
Gnomad4 EAS exome
AF:
0.898
Gnomad4 SAS exome
AF:
0.960
Gnomad4 FIN exome
AF:
0.993
Gnomad4 NFE exome
AF:
0.999
Gnomad4 OTH exome
AF:
0.983
GnomAD4 genome
AF:
0.965
AC:
147082
AN:
152348
Hom.:
71128
Cov.:
34
AF XY:
0.964
AC XY:
71840
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.924
Gnomad4 AMR
AF:
0.919
Gnomad4 ASJ
AF:
0.999
Gnomad4 EAS
AF:
0.903
Gnomad4 SAS
AF:
0.965
Gnomad4 FIN
AF:
0.995
Gnomad4 NFE
AF:
0.999
Gnomad4 OTH
AF:
0.971
Alfa
AF:
0.970
Hom.:
10729
Bravo
AF:
0.956
Asia WGS
AF:
0.924
AC:
3214
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Nov 12, 2018
GeneDx
Significance: 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
-0.46
CADD
Benign
6.8
DANN
Benign
0.95

Splicing

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.

Other links and lift over

dbSNP: rs541154; hg19: chr8-102504541; API