rs3791749

Positions:

• chr2-9999636-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198182.3(GRHL1):​c.1742+607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,138 control chromosomes in the GnomAD database, including 19,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19790 hom., cov: 33)
• Consequence: GRHL1 NM_198182.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

Genes affected

GRHL1 (HGNC:17923): (grainyhead like transcription factor 1) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009]

ENSG00000289033 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL1	NM_198182.3	c.1742+607T>C		intron_variant		ENST00000324907.14	NP_937825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL1	ENST00000324907.14	c.1742+607T>C		intron_variant		1	NM_198182.3	ENSP00000324693.9

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76048 AN: 152020 Hom.: 19761 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.500 AC: 76130 AN: 152138 Hom.: 19790 Cov.: 33 AF XY: 0.500 AC XY: 37165 AN XY: 74362

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.498

Alfa AF: 0.445 Hom.: 14041

Bravo AF: 0.521

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.4
DANN	Benign	0.55

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: rs3791749; hg19: chr2-10139764;