rs12407356

Positions:

• chr1-24251521-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.24251521G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000690803.1	c.-76+14684G>A		intron_variant				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

Gnomad4 AFR AF: 0.00517

Gnomad4 AMR AF: 0.0669

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0344 Hom.: 26

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12407356; hg19: chr1-24578011;