1-24331370-A-G

Position:

• chr1-24331370-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198173.3(GRHL3):​c.18-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,503,844 control chromosomes in the GnomAD database, including 23,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3520 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20334 hom.)
• Consequence: GRHL3 NM_198173.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-24331370-A-G is Benign according to our data. Variant chr1-24331370-A-G is described in ClinVar as [Benign]. Clinvar id is 1258052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL3	NM_198173.3	c.18-56A>G		intron_variant		ENST00000361548.9	NP_937816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000361548.9	c.18-56A>G		intron_variant		1	NM_198173.3	ENSP00000354943	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30492 AN: 152038 Hom.: 3512 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.170 AC: 229665 AN: 1351688 Hom.: 20334 AF XY: 0.168 AC XY: 111965 AN XY: 665584

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.201 AC: 30512 AN: 152156 Hom.: 3520 Cov.: 32 AF XY: 0.197 AC XY: 14629 AN XY: 74404

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.171

Alfa AF: 0.161 Hom.: 3318

Bravo AF: 0.206

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.041
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2486669; hg19: chr1-24657860; COSMIC: COSV52571283;