rs6989650

Positions:

• chr8-101669109-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.*2406C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,982 control chromosomes in the GnomAD database, including 4,625 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 0.24 (4625 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: GRHL2 NM_024915.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.*2406C>T		3_prime_UTR_variant	16/16	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.*2406C>T		3_prime_UTR_variant	16/16		NP_001317522.1
GRHL2	XM_011517306.4	c.*2406C>T		3_prime_UTR_variant	16/16		XP_011515608.1
GRHL2	XM_011517307.4	c.1763+4591C>T		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.*2406C>T		3_prime_UTR_variant	16/16		NM_024915.4	ENSP00000495564	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36752 AN: 151860 Hom.: 4625 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.242 AC: 36772 AN: 151978 Hom.: 4625 Cov.: 32 AF XY: 0.243 AC XY: 18079 AN XY: 74272

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.227

Alfa AF: 0.220 Hom.: 6477

Bravo AF: 0.247

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.82

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: rs6989650; hg19: chr8-102681337;