Variant rs3735713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024915.4(GRHL2):c.*41G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,158,186 control chromosomes in the GnomAD database, including 80,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11171 hom., cov: 31)

Exomes 𝑓: 0.36 ( 69449 hom. )

Consequence

GRHL2
NM_024915.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.369

Variant links:

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]

GRHL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 8-101666744-G-A is Benign according to our data. Variant chr8-101666744-G-A is described in ClinVar as [Benign]. Clinvar id is 1260503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
GRHL2	NM_024915.4 linkuse as main transcript	c.*41G>A	3_prime_UTR_variant	16/16	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2 linkuse as main transcript	c.*41G>A	3_prime_UTR_variant	16/16		NP_001317522.1
GRHL2	XM_011517306.4 linkuse as main transcript	c.*41G>A	3_prime_UTR_variant	16/16		XP_011515608.1
GRHL2	XM_011517307.4 linkuse as main transcript	c.1763+2226G>A	intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1 linkuse as main transcript	c.*41G>A		3_prime_UTR_variant	16/16		NM_024915.4	ENSP00000495564	P1	Q6ISB3-1
GRHL2	ENST00000395927.1 linkuse as main transcript	c.*41G>A		3_prime_UTR_variant	16/16	2		ENSP00000379260		Q6ISB3-2

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57413

AN:

151816

Hom.:

11153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.391

AC:

94688

AN:

242274

Hom.:

18994

AF XY:

0.393

AC XY:

51284

AN XY:

130558

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.362

AC:

364580

AN:

1006252

Hom.:

69449

Cov.:

AF XY:

0.368

AC XY:

191770

AN XY:

520616

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.378

AC:

57473

AN:

151934

Hom.:

11171

Cov.:

AF XY:

0.381

AC XY:

28274

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.541

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.354

Hom.:

10314

Bravo

AF:

0.382

Asia WGS

AF:

0.516

AC:

1794

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Corneal dystrophy, posterior polymorphous, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Autosomal dominant nonsyndromic hearing loss 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.27

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over