chr2-9977740-C-T

Position:

• chr2-9977740-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL1	NM_198182.3	c.1111-8384C>T		intron_variant		ENST00000324907.14	NP_937825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL1	ENST00000324907.14	c.1111-8384C>T		intron_variant		1	NM_198182.3	ENSP00000324693	P1
GRHL1	ENST00000405379.6	c.544-8384C>T		intron_variant		1		ENSP00000384209
GRHL1	ENST00000472167.5	c.1111-8384C>T		intron_variant, NMD_transcript_variant		1		ENSP00000418275
GRHL1	ENST00000464418.5	c.*353-8384C>T		intron_variant, NMD_transcript_variant		2		ENSP00000420654

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

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.371

Alfa AF: 0.310 Hom.: 8838

Bravo AF: 0.378

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.32

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: rs11902236; hg19: chr2-10117868;