rs476321

Positions:

• chr8-101497571-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.20+4782C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,066 control chromosomes in the GnomAD database, including 5,679 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 0.27 (5679 hom., cov: 32)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.20+4782C>T		intron_variant		ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.-29+4722C>T		intron_variant			NP_001317522.1
GRHL2	XM_011517306.4	c.-29+4985C>T		intron_variant			XP_011515608.1
GRHL2	XM_011517307.4	c.20+4782C>T		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+4782C>T		intron_variant			NM_024915.4	ENSP00000495564	P1
GRHL2	ENST00000472106.2	n.348+4782C>T		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-29+4722C>T		intron_variant		2		ENSP00000379260

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40655 AN: 151948 Hom.: 5667 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.268 AC: 40697 AN: 152066 Hom.: 5679 Cov.: 32 AF XY: 0.269 AC XY: 19999 AN XY: 74346

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.274

Alfa AF: 0.237 Hom.: 5996

Bravo AF: 0.272

Asia WGS AF: 0.354 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.67

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: rs476321; hg19: chr8-102509799;