rs12407356

Variant names:

• chr1-24251521-G-A
• rs12407356
• ENST00000690803.1:c.-76+14684G>A

Variant summary

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

The ENST00000690803.1(GRHL3):​c.-76+14684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,268 control chromosomes in the GnomAD database, including 168 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 0.034 (168 hom., cov: 32)
• Consequence: GRHL3 ENST00000690803.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0635 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+14684G>A		intron_variant	Intron 2 of 15			ENSP00000510783.1

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5117 AN: 152150 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.00519

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0248

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

GnomAD4 genome AF: 0.0336 AC: 5122 AN: 152268 Hom.: 168 Cov.: 32 AF XY: 0.0375 AC XY: 2795 AN XY: 74452

African (AFR) AF: 0.00517 AC: 215 AN: 41558

American (AMR) AF: 0.0669 AC: 1023 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.0226 AC: 109 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1281 AN: 10588

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2303 AN: 68010

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0299 Hom.: 80

Bravo AF: 0.0278

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.47
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs12407356; hg19: chr1-24578011;