rs3735714

Positions:

• chr8-101667094-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.*391C>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 0.38 in 295,770 control chromosomes in the GnomAD database, including 22,517 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 0.39 (11873 hom., cov: 32)
  • Exomes 𝑓: 0.37 (10644 hom.)
• Consequence: GRHL2 NM_024915.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.*391C>T		3_prime_UTR_variant	16/16	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.*391C>T		3_prime_UTR_variant	16/16		NP_001317522.1
GRHL2	XM_011517306.4	c.*391C>T		3_prime_UTR_variant	16/16		XP_011515608.1
GRHL2	XM_011517307.4	c.1763+2576C>T		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.*391C>T		3_prime_UTR_variant	16/16		NM_024915.4	ENSP00000495564	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59074 AN: 151926 Hom.: 11855 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.370 AC: 53116 AN: 143726 Hom.: 10644 Cov.: 0 AF XY: 0.379 AC XY: 28257 AN XY: 74582

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.389 AC: 59136 AN: 152044 Hom.: 11873 Cov.: 32 AF XY: 0.392 AC XY: 29092 AN XY: 74302

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.384

Alfa AF: 0.368 Hom.: 4062

Bravo AF: 0.395

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.87
DANN	Benign	0.58

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: rs3735714; hg19: chr8-102679322;