8-101493429-CCCCTCCCCCGCCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024915.4(GRHL2):c.20+651_20+663del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49803 hom., cov: 0)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.971

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 -10 ACMG points.

• BP6: Variant 8-101493429-CCCCTCCCCCGCCT-C is Benign according to our data. Variant chr8-101493429-CCCCTCCCCCGCCT-C is described in ClinVar as [Benign]. Clinvar id is 1246996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.20+651_20+663del		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.-29+591_-29+603del		intron_variant
GRHL2	XM_011517306.4	c.-29+854_-29+866del		intron_variant
GRHL2	XM_011517307.4	c.20+651_20+663del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+651_20+663del		intron_variant			NM_024915.4	P1
GRHL2	ENST00000472106.2	n.348+651_348+663del		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-29+591_-29+603del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.798 AC: 120456 AN: 151020 Hom.: 49802 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.983

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.797 AC: 120490 AN: 151132 Hom.: 49803 Cov.: 0 AF XY: 0.797 AC XY: 58823 AN XY: 73818

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.819

Alfa AF: 0.845 Hom.: 5980

Bravo AF: 0.776

Asia WGS AF: 0.728 AC: 2506 AN: 3442

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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71276976; hg19: chr8-102505657;