1-24319897-C-A

Position:

• chr1-24319897-C-A

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.17+329C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 438,652 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (190 hom., cov: 32)
  • Exomes 𝑓: 0.052 (486 hom.)
• Consequence: GRHL3 NM_198173.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.323

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-AS1 (HGNC:41119): (GRHL3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-24319897-C-A is Benign according to our data. Variant chr1-24319897-C-A is described in ClinVar as [Benign]. Clinvar id is 1280059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL3	NM_198173.3	c.17+329C>A		intron_variant		ENST00000361548.9	NP_937816.1
GRHL3-AS1	NR_183722.1	n.326+1769G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000361548.9	c.17+329C>A		intron_variant		1	NM_198173.3	ENSP00000354943	P1
GRHL3-AS1	ENST00000437965.1	n.236+1769G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6246 AN: 152184 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.0519 AC: 14852 AN: 286350 Hom.: 486 Cov.: 5 AF XY: 0.0500 AC XY: 7531 AN XY: 150610

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.0410 AC: 6243 AN: 152302 Hom.: 190 Cov.: 32 AF XY: 0.0395 AC XY: 2944 AN XY: 74470

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0574 Hom.: 78

Bravo AF: 0.0370

Asia WGS AF: 0.0120 AC: 40 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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs79338443; hg19: chr1-24646387;