rs6670533

Variant names:

• chr1-24258000-G-A
• rs6670533
• ENST00000690803.1:c.-76+21163G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-24258000-G-A
• chr1-24258000-G-C
• chr1-24258000-G-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+21163G>A variant causes a intron change. The variant allele was found at a frequency of 0.0872 in 152,286 control chromosomes in the GnomAD database, including 643 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 0.087 (643 hom., cov: 32)
• Consequence: GRHL3 ENST00000690803.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 7 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 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+21163G>A		intron_variant	Intron 2 of 15			ENSP00000510783.1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13247 AN: 152168 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0872 AC: 13273 AN: 152286 Hom.: 643 Cov.: 32 AF XY: 0.0850 AC XY: 6332 AN XY: 74472

African (AFR) AF: 0.124 AC: 5134 AN: 41556

American (AMR) AF: 0.0647 AC: 990 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0476 AC: 230 AN: 4830

European-Finnish (FIN) AF: 0.0902 AC: 956 AN: 10604

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0779 AC: 5300 AN: 68012

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0779 Hom.: 1131

Bravo AF: 0.0861

Asia WGS AF: 0.0310 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.41
PhyloP100		4.3

Splicing

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

Other links and lift over

dbSNP: rs6670533; hg19: chr1-24584490;