rs10794657

Variant names:

• chr1-24299684-A-G
• rs10794657
• ENST00000690803.1:c.-75-34961A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-24299684-A-G
• chr1-24299684-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690803.1(GRHL3):​c.-75-34961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,094 control chromosomes in the GnomAD database, including 44,307 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (44307 hom., cov: 33)
• Consequence: GRHL3 ENST00000690803.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 6 publications found

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]

GRHL3 Gene-Disease associations (from GenCC):

• van der Woude syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• van der Woude syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000690803.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL3	ENST00000690803.1		c.-75-34961A>G		intron	N/A	ENSP00000510783.1	Q8TE85-4

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114520 AN: 151976 Hom.: 44275 Cov.: 33

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.753 AC: 114599 AN: 152094 Hom.: 44307 Cov.: 33 AF XY: 0.757 AC XY: 56255 AN XY: 74344

African (AFR) AF: 0.573 AC: 23770 AN: 41454

American (AMR) AF: 0.840 AC: 12842 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2638 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5182

South Asian (SAS) AF: 0.913 AC: 4409 AN: 4830

European-Finnish (FIN) AF: 0.744 AC: 7866 AN: 10570

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55254 AN: 67992

Other (OTH) AF: 0.762 AC: 1607 AN: 2108

Alfa AF: 0.782 Hom.: 5891

Bravo AF: 0.753

Asia WGS AF: 0.922 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10794657; hg19: chr1-24626174;