rs3824090

Positions:

• chr8-101666988-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024915.4(GRHL2):​c.*285C>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 0.236 in 523,474 control chromosomes in the GnomAD database, including 15,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4562 hom., cov: 32)
  • Exomes 𝑓: 0.23 (10565 hom.)
• Consequence: GRHL2 NM_024915.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.284

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-101666988-C-T is Benign according to our data. Variant chr8-101666988-C-T is described in ClinVar as [Benign]. Clinvar id is 1261948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.*285C>T		3_prime_UTR_variant	16/16	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.*285C>T		3_prime_UTR_variant	16/16		NP_001317522.1
GRHL2	XM_011517306.4	c.*285C>T		3_prime_UTR_variant	16/16		XP_011515608.1
GRHL2	XM_011517307.4	c.1763+2470C>T		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.*285C>T		3_prime_UTR_variant	16/16		NM_024915.4	ENSP00000495564.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36608 AN: 151816 Hom.: 4562 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.234 AC: 86758 AN: 371540 Hom.: 10565 Cov.: 0 AF XY: 0.237 AC XY: 46540 AN XY: 196760

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.241 AC: 36627 AN: 151934 Hom.: 4562 Cov.: 32 AF XY: 0.242 AC XY: 17990 AN XY: 74244

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.227

Alfa AF: 0.214 Hom.: 3213

Bravo AF: 0.247

Asia WGS AF: 0.262 AC: 915 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.61

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: rs3824090; hg19: chr8-102679216;