rs12143309

chr1-24267934-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690803.1(GRHL3):c.-76+31097C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,110 control chromosomes in the GnomAD database, including 13,446 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 0.39 (13446 hom., cov: 33)
• Consequence: GRHL3 ENST00000690803.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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.-76+31097C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59893 AN: 151992 Hom.: 13449 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.394 AC: 59891 AN: 152110 Hom.: 13446 Cov.: 33 AF XY: 0.393 AC XY: 29197 AN XY: 74352

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.417

Alfa AF: 0.444 Hom.: 1999

Bravo AF: 0.379

Asia WGS AF: 0.420 AC: 1458 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	1.1
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12143309; hg19: chr1-24594424; COSMIC: COSV59931837;