1-24336413-G-C

Position:

• chr1-24336413-G-C

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.267-69G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,002,358 control chromosomes in the GnomAD database, including 6,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1613 hom., cov: 31)
  • Exomes 𝑓: 0.10 (5044 hom.)
• Consequence: GRHL3 NM_198173.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.958

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=-0.95).
• BP6: Variant 1-24336413-G-C is Benign according to our data. Variant chr1-24336413-G-C is described in ClinVar as [Benign]. Clinvar id is 1276904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL3	NM_198173.3	c.267-69G>C		intron_variant		ENST00000361548.9	NP_937816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000361548.9	c.267-69G>C		intron_variant		1	NM_198173.3	ENSP00000354943	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19833 AN: 151704 Hom.: 1610 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0630

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0996 AC: 84703 AN: 850536 Hom.: 5044 AF XY: 0.0968 AC XY: 41846 AN XY: 432506

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.0630

Gnomad4 EAS exome AF: 0.000247

Gnomad4 SAS exome AF: 0.0298

Gnomad4 FIN exome AF: 0.0965

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0960

GnomAD4 genome AF: 0.131 AC: 19877 AN: 151822 Hom.: 1613 Cov.: 31 AF XY: 0.125 AC XY: 9254 AN XY: 74206

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0630

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0281

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.112

Alfa AF: 0.133 Hom.: 189

Bravo AF: 0.133

Asia WGS AF: 0.0350 AC: 122 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.38

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: rs12062028; hg19: chr1-24662903;