rs12143309

Variant names:

• chr1-24267934-C-T
• rs12143309
• ENST00000690803.1:c.-76+31097C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000690803.1	c.-76+31097C>T		intron_variant	Intron 2 of 15			ENSP00000510783.1

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;