1-24334426-C-T

Position:

• chr1-24334426-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198173.3(GRHL3):​c.205-219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,972 control chromosomes in the GnomAD database, including 1,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1665 hom., cov: 31)
• Consequence: GRHL3 NM_198173.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-24334426-C-T is Benign according to our data. Variant chr1-24334426-C-T is described in ClinVar as [Benign]. Clinvar id is 1229943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL3	NM_198173.3	c.205-219C>T		intron_variant		ENST00000361548.9	NP_937816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000361548.9	c.205-219C>T		intron_variant		1	NM_198173.3	ENSP00000354943	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20599 AN: 151854 Hom.: 1664 Cov.: 31

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20611 AN: 151972 Hom.: 1665 Cov.: 31 AF XY: 0.134 AC XY: 9945 AN XY: 74262

Gnomad4 AFR AF: 0.0629

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.137

Alfa AF: 0.158 Hom.: 268

Bravo AF: 0.126

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-1.0
CADD	Benign	0.68
DANN	Benign	0.86

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: rs61772766; hg19: chr1-24660916;