dbSNP rs79338443: GRHL3:c.17+329C>A (chr1-24319897-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198173.3(GRHL3):c.17+329C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 438,652 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 190 hom., cov: 32)

Exomes 𝑓: 0.052 ( 486 hom. )

Consequence

GRHL3
NM_198173.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.323

Publications

3 publications found

Variant links:

Genes affected

GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

GRHL3 links:

GRHL3-AS1 (HGNC:41119): (GRHL3 antisense RNA 1)

GRHL3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-24319897-C-A is Benign according to our data. Variant chr1-24319897-C-A is described in ClinVar as Benign. ClinVar VariationId is 1280059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198173.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRHL3	NM_198173.3	MANE Select	c.17+329C>A	intron	N/A	NP_937816.1	Q8TE85-5
GRHL3	NM_198174.3		c.17+329C>A	intron	N/A	NP_937817.3
GRHL3	NM_001195010.2		c.-122+150C>A	intron	N/A	NP_001181939.1	Q8TE85-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRHL3	ENST00000361548.9	TSL:1 MANE Select	c.17+329C>A	intron	N/A	ENSP00000354943.5	Q8TE85-5
GRHL3	ENST00000356046.6	TSL:1	c.-122+150C>A	intron	N/A	ENSP00000348333.2	Q8TE85-3
GRHL3	ENST00000524724.6	TSL:4	c.-166C>A	5_prime_UTR	Exon 1 of 16	ENSP00000431290.2	Q8TE85-3

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6246

AN:

152184

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0392

GnomAD4 exome

AF:

0.0519

AC:

14852

AN:

286350

Hom.:

486

Cov.:

AF XY:

0.0500

AC XY:

7531

AN XY:

150610

show subpopulations

African (AFR)

AF:

0.0100

AC:

AN:

8262

American (AMR)

AF:

0.0254

AC:

323

AN:

12708

Ashkenazi Jewish (ASJ)

AF:

0.0477

AC:

360

AN:

7542

East Asian (EAS)

AF:

0.00

AC:

AN:

14222

South Asian (SAS)

AF:

0.0202

AC:

733

AN:

36292

European-Finnish (FIN)

AF:

0.0756

AC:

921

AN:

12180

Middle Eastern (MID)

AF:

0.0403

AC:

AN:

1118

European-Non Finnish (NFE)

AF:

0.0649

AC:

11621

AN:

179070

Other (OTH)

AF:

0.0512

AC:

766

AN:

14956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

688

1375

2063

2750

3438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.0410

AC:

6243

AN:

152302

Hom.:

190

Cov.:

AF XY:

0.0395

AC XY:

2944

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0105

AC:

438

AN:

41576

American (AMR)

AF:

0.0252

AC:

386

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0168

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0677

AC:

718

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4330

AN:

68022

Other (OTH)

AF:

0.0383

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

306

612

918

1224

1530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0518

Hom.:

105

Bravo

AF:

0.0370

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.64

PhyloP100

0.32

PromoterAI

-0.0012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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