Variant 2-9955068-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_198182.3(GRHL1):c.174C>G(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,390 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 19 hom. )

Consequence

GRHL1
NM_198182.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.12

Variant links:

Genes affected

GRHL1 (HGNC:17923): (grainyhead like transcription factor 1) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009]

GRHL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-9955068-C-G is Benign according to our data. Variant chr2-9955068-C-G is described in ClinVar as [Benign]. Clinvar id is 785957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.12 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00932 (1419/152288) while in subpopulation AFR AF= 0.0317 (1315/41544). AF 95% confidence interval is 0.0302. There are 18 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1419 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL1	NM_198182.3 link	c.174C>G	p.Ala58Ala	synonymous_variant	2/16	ENST00000324907.14	NP_937825.2	Q9NZI5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL1	ENST00000324907.14 link	c.174C>G	p.Ala58Ala	synonymous_variant	2/16	1	NM_198182.3	ENSP00000324693.9		Q9NZI5-1

Frequencies

GnomAD3 genomes

AF:

0.00924

AC:

1406

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00252

AC:

626

AN:

248792

Hom.:

AF XY:

0.00186

AC XY:

251

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.00105

AC:

1529

AN:

1461102

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

685

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.00932

AC:

1419

AN:

152288

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.000734

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.010

DANN

Benign

0.47

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