Variant rs727504472 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_024915.4(GRHL2):c.285-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,613,572 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 70 hom. )

Consequence

GRHL2
NM_024915.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.284

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 -16 ACMG points.

BP6

Variant 8-101558399-CG-C is Benign according to our data. Variant chr8-101558399-CG-C is described in ClinVar as [Benign]. Clinvar id is 178828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00568 (865/152176) while in subpopulation NFE AF= 0.00906 (616/68010). AF 95% confidence interval is 0.00847. There are 3 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GRHL2	NM_024915.4 linkuse as main transcript	c.285-14del	intron_variant	ENST00000646743.1
GRHL2	NM_001330593.2 linkuse as main transcript	c.237-14del	intron_variant
GRHL2	XM_011517306.4 linkuse as main transcript	c.237-14del	intron_variant
GRHL2	XM_011517307.4 linkuse as main transcript	c.285-14del	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1 linkuse as main transcript	c.285-14del		intron_variant			NM_024915.4	P1	Q6ISB3-1
GRHL2	ENST00000395927.1 linkuse as main transcript	c.237-14del		intron_variant		2			Q6ISB3-2

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

866

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00642

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00529

AC:

1328

AN:

251216

Hom.:

AF XY:

0.00509

AC XY:

691

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.00857

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00809

AC:

11824

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

5650

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00483

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00571

Gnomad4 NFE exome

AF:

0.00964

Gnomad4 OTH exome

AF:

0.00797

GnomAD4 genome

AF:

0.00568

AC:

865

AN:

152176

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00733

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00642

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00527

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 13, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 04, 2016

c.285-14delG in intron 3 of GRHL2: This variant is not expected to have clinical significance because it has been identified in 0.74% (491/66712) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs559133364). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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