rs6988306

chr8-101583982-C-T

Variant summary

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

The NM_024915.4(GRHL2):c.1003+6463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,188 control chromosomes in the GnomAD database, including 1,154 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 0.12 (1154 hom., cov: 32)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.1003+6463C>T		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.955+6463C>T		intron_variant
GRHL2	XM_011517306.4	c.955+6463C>T		intron_variant
GRHL2	XM_011517307.4	c.1003+6463C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.1003+6463C>T		intron_variant			NM_024915.4	P1
GRHL2	ENST00000395927.1	c.955+6463C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18379 AN: 152070 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.121 AC: 18414 AN: 152188 Hom.: 1154 Cov.: 32 AF XY: 0.121 AC XY: 9011 AN XY: 74414

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.141

Alfa AF: 0.135 Hom.: 1494

Bravo AF: 0.120

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.97
Dann	Benign	0.66

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: rs6988306; hg19: chr8-102596210;