rs666026

Positions:

• chr8-101544990-C-A
• chr8-101544990-C-G

Variant summary

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

The NM_024915.4(GRHL2):​c.216+1554C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,106 control chromosomes in the GnomAD database, including 62,215 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 0.90 (62215 hom., cov: 31)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

Genes affected

GRHL2 (HGNC:2799): (grainyhead like transcription factor 2) The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.216+1554C>A		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.168+1554C>A		intron_variant
GRHL2	XM_011517306.4	c.168+1554C>A		intron_variant
GRHL2	XM_011517307.4	c.216+1554C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.216+1554C>A		intron_variant			NM_024915.4	P1
GRHL2	ENST00000395927.1	c.168+1554C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137228 AN: 151990 Hom.: 62161 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.903 AC: 137335 AN: 152106 Hom.: 62215 Cov.: 31 AF XY: 0.901 AC XY: 66995 AN XY: 74326

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.937

Gnomad4 OTH AF: 0.900

Alfa AF: 0.928 Hom.: 85788

Bravo AF: 0.900

Asia WGS AF: 0.803 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.60

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: rs666026; hg19: chr8-102557218;