8-101543073-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024915.4(GRHL2):c.21-168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,188 control chromosomes in the GnomAD database, including 16,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (16100 hom., cov: 33)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-101543073-A-G is Benign according to our data. Variant chr8-101543073-A-G is described in ClinVar as [Benign]. Clinvar id is 1286039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.21-168A>G		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.-28-168A>G		intron_variant
GRHL2	XM_011517306.4	c.-28-168A>G		intron_variant
GRHL2	XM_011517307.4	c.21-168A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.21-168A>G		intron_variant			NM_024915.4	P1
GRHL2	ENST00000472106.2	n.349-168A>G		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-28-168A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64498 AN: 152070 Hom.: 16102 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64510 AN: 152188 Hom.: 16100 Cov.: 33 AF XY: 0.424 AC XY: 31559 AN XY: 74394

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.439

Alfa AF: 0.502 Hom.: 4856

Bravo AF: 0.405

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.94
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs6984360; hg19: chr8-102555301;