rs116154722

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_024915.4(GRHL2):c.*6G>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 0.000389 in 1,575,746 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

GRHL2
NM_024915.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.370

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 28
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AD Classification: STRONG Submitted by: ClinGen
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital fibrosis of extraocular muscles
Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

GRHL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-101666709-G-A is Benign according to our data. Variant chr8-101666709-G-A is described in ClinVar as Benign. ClinVar VariationId is 46213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00212 (323/152250) while in subpopulation AFR AF = 0.00741 (308/41550). AF 95% confidence interval is 0.00673. There are 1 homozygotes in GnomAd4. There are 165 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024915.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GRHL2	NM_024915.4	MANE Select	c.*6G>A	3_prime_UTR	Exon 16 of 16	NP_079191.2
GRHL2	NM_001330593.2		c.*6G>A	3_prime_UTR	Exon 16 of 16	NP_001317522.1
GRHL2	NM_001440448.1		c.*6G>A	3_prime_UTR	Exon 16 of 16	NP_001427377.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GRHL2	ENST00000646743.1	MANE Select	c.*6G>A	3_prime_UTR	Exon 16 of 16	ENSP00000495564.1
GRHL2	ENST00000395927.1	TSL:2	c.*6G>A	3_prime_UTR	Exon 16 of 16	ENSP00000379260.1
GRHL2	ENST00000907653.1		c.*6G>A	3_prime_UTR	Exon 14 of 14	ENSP00000577712.1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00741

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000510

AC:

128

AN:

250998

AF XY:

0.000347

show subpopulations

Gnomad AFR exome

AF:

0.00721

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000204

AC:

290

AN:

1423496

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

111

AN XY:

710802

show subpopulations

African (AFR)

AF:

0.00737

AC:

241

AN:

32708

American (AMR)

AF:

0.000358

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25902

East Asian (EAS)

AF:

0.00

AC:

AN:

39526

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077086

Other (OTH)

AF:

0.000491

AC:

AN:

59068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00212

AC:

323

AN:

152250

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00741

AC:

308

AN:

41550

American (AMR)

AF:

0.000785

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00234

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.0

(source)

DANN

Benign

0.63

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over