8-101493477-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.20+688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 150,206 control chromosomes in the GnomAD database, including 50,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (50673 hom., cov: 30)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.814

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=-0.55).
• BP6: Variant 8-101493477-A-G is Benign according to our data. Variant chr8-101493477-A-G is described in ClinVar as [Benign]. Clinvar id is 1243960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.20+688A>G		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.-29+628A>G		intron_variant
GRHL2	XM_011517306.4	c.-29+891A>G		intron_variant
GRHL2	XM_011517307.4	c.20+688A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+688A>G		intron_variant			NM_024915.4	P1
GRHL2	ENST00000472106.2	n.348+688A>G		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-29+628A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 121848 AN: 150126 Hom.: 50672 Cov.: 30

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.983

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.811 AC: 121880 AN: 150206 Hom.: 50673 Cov.: 30 AF XY: 0.810 AC XY: 59488 AN XY: 73406

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.834

Alfa AF: 0.860 Hom.: 6615

Bravo AF: 0.784

Asia WGS AF: 0.732 AC: 2527 AN: 3454

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

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	10
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs581752; hg19: chr8-102505705;