rs6670533

chr1-24258000-G-Achr1-24258000-G-Cchr1-24258000-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL3	ENST00000690803.1	c.-76+21163G>A		intron_variant

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0647

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0779

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0741 Hom.: 561

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6670533; hg19: chr1-24584490;