rs12143309

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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.-76+31097C>T		intron	N/A	ENSP00000510783.1	Q8TE85-4

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

African (AFR) AF: 0.165 AC: 6840 AN: 41510

American (AMR) AF: 0.379 AC: 5799 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1822 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5174

South Asian (SAS) AF: 0.473 AC: 2279 AN: 4818

European-Finnish (FIN) AF: 0.454 AC: 4798 AN: 10570

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34605 AN: 67964

Other (OTH) AF: 0.417 AC: 881 AN: 2114

Alfa AF: 0.433 Hom.: 2010

Bravo AF: 0.379

Asia WGS AF: 0.420 AC: 1458 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	1.1
DANN	Benign	0.40
PhyloP100		-0.68

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12143309;

hg19: chr1-24594424;

COSMIC: COSV59931837;