1-24299684-A-G

Position:

• chr1-24299684-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL3	ENST00000690803.1	c.-75-34961A>G		intron_variant

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

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.762

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10794657; hg19: chr1-24626174;