chr1-24319888-G-A

Position:

• chr1-24319888-G-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+320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 499,544 control chromosomes in the GnomAD database, including 3,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2827 hom., cov: 32)
  • Exomes 𝑓: 0.013 (659 hom.)
• Consequence: GRHL3 NM_198173.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.211

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=-0.86).
• BP6: Variant 1-24319888-G-A is Benign according to our data. Variant chr1-24319888-G-A is described in ClinVar as [Benign]. Clinvar id is 1273621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL3	NM_198173.3	c.17+320G>A		intron_variant		ENST00000361548.9
GRHL3-AS1	NR_183722.1	n.326+1778C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL3	ENST00000361548.9	c.17+320G>A		intron_variant		1	NM_198173.3	P1
GRHL3-AS1	ENST00000437965.1	n.236+1778C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15956 AN: 152086 Hom.: 2815 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0131 AC: 4533 AN: 347340 Hom.: 659 Cov.: 6 AF XY: 0.0112 AC XY: 2041 AN XY: 181856

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.00355

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000790

Gnomad4 OTH exome AF: 0.0224

GnomAD4 genome AF: 0.105 AC: 15999 AN: 152204 Hom.: 2827 Cov.: 32 AF XY: 0.101 AC XY: 7529 AN XY: 74444

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.101 Hom.: 283

Bravo AF: 0.121

Asia WGS AF: 0.0230 AC: 81 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	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.64

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: rs2247991; hg19: chr1-24646378;