rs3791749

Variant names:

• chr2-9999636-T-C
• rs3791749
• NM_198182.3:c.1742+607T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198182.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL1	NM_198182.3	MANE Select	c.1742+607T>C		intron	N/A	NP_937825.2	Q9NZI5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL1	ENST00000324907.14	TSL:1 MANE Select	c.1742+607T>C		intron	N/A	ENSP00000324693.9	Q9NZI5-1
	GRHL1	ENST00000405379.6	TSL:1	c.1175+607T>C		intron	N/A	ENSP00000384209.3	Q9NZI5-2
	GRHL1	ENST00000472167.5	TSL:1	n.*232+607T>C		intron	N/A	ENSP00000418275.1	Q9NZI5-3

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

African (AFR) AF: 0.639 AC: 26535 AN: 41510

American (AMR) AF: 0.549 AC: 8388 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5178

South Asian (SAS) AF: 0.357 AC: 1724 AN: 4824

European-Finnish (FIN) AF: 0.440 AC: 4647 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29387 AN: 67982

Other (OTH) AF: 0.498 AC: 1051 AN: 2112

Alfa AF: 0.446 Hom.: 14962

Bravo AF: 0.521

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.4
DANN	Benign	0.55
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3791749; hg19: chr2-10139764;