chr1-24322926-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198173.3(GRHL3):​c.17+3358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 624,322 control chromosomes in the GnomAD database, including 4,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1746 hom., cov: 32)
Exomes 𝑓: 0.11 ( 3075 hom. )

Consequence

GRHL3
NM_198173.3 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.827
Variant links:
Genes affected
GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

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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 1-24322926-C-T is Benign according to our data. Variant chr1-24322926-C-T is described in ClinVar as [Benign]. Clinvar id is 1243060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRHL3NM_198173.3 linkuse as main transcriptc.17+3358C>T intron_variant ENST00000361548.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRHL3ENST00000361548.9 linkuse as main transcriptc.17+3358C>T intron_variant 1 NM_198173.3 P1Q8TE85-5

Frequencies

GnomAD3 genomes
AF:
0.139
AC:
21195
AN:
152056
Hom.:
1740
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.225
Gnomad AMI
AF:
0.0987
Gnomad AMR
AF:
0.0999
Gnomad ASJ
AF:
0.0421
Gnomad EAS
AF:
0.159
Gnomad SAS
AF:
0.108
Gnomad FIN
AF:
0.112
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.116
GnomAD4 exome
AF:
0.109
AC:
51269
AN:
472148
Hom.:
3075
AF XY:
0.108
AC XY:
27113
AN XY:
249902
show subpopulations
Gnomad4 AFR exome
AF:
0.217
Gnomad4 AMR exome
AF:
0.0962
Gnomad4 ASJ exome
AF:
0.0429
Gnomad4 EAS exome
AF:
0.127
Gnomad4 SAS exome
AF:
0.103
Gnomad4 FIN exome
AF:
0.113
Gnomad4 NFE exome
AF:
0.106
Gnomad4 OTH exome
AF:
0.114
GnomAD4 genome
AF:
0.139
AC:
21207
AN:
152174
Hom.:
1746
Cov.:
32
AF XY:
0.136
AC XY:
10142
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.224
Gnomad4 AMR
AF:
0.100
Gnomad4 ASJ
AF:
0.0421
Gnomad4 EAS
AF:
0.159
Gnomad4 SAS
AF:
0.108
Gnomad4 FIN
AF:
0.112
Gnomad4 NFE
AF:
0.108
Gnomad4 OTH
AF:
0.114
Alfa
AF:
0.121
Hom.:
572
Bravo
AF:
0.144
Asia WGS
AF:
0.136
AC:
472
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
Benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.3
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1324663; hg19: chr1-24649416; COSMIC: COSV52565504; COSMIC: COSV52565504; API