chr2-9977740-C-T

Variant names:

• chr2-9977740-C-T
• rs11902236
• NM_198182.3:c.1111-8384C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198182.3(GRHL1):​c.1111-8384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,044 control chromosomes in the GnomAD database, including 11,825 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 0.36 (11825 hom., cov: 32)
• Consequence: GRHL1 NM_198182.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 50 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 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.1111-8384C>T		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.1111-8384C>T		intron	N/A	ENSP00000324693.9	Q9NZI5-1
	GRHL1	ENST00000405379.6	TSL:1	c.544-8384C>T		intron	N/A	ENSP00000384209.3	Q9NZI5-2
	GRHL1	ENST00000472167.5	TSL:1	n.1111-8384C>T		intron	N/A	ENSP00000418275.1	Q9NZI5-3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54050 AN: 151926 Hom.: 11795 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.356 AC: 54129 AN: 152044 Hom.: 11825 Cov.: 32 AF XY: 0.345 AC XY: 25675 AN XY: 74326

African (AFR) AF: 0.612 AC: 25341 AN: 41432

American (AMR) AF: 0.247 AC: 3766 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3470

East Asian (EAS) AF: 0.142 AC: 736 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1511 AN: 10588

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19217 AN: 67980

Other (OTH) AF: 0.371 AC: 782 AN: 2106

Alfa AF: 0.315 Hom.: 26077

Bravo AF: 0.378

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.32
PhyloP100		-0.27
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: rs11902236; hg19: chr2-10117868;