8-101493561-C-T

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+772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 152,206 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.025 (78 hom., cov: 33)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.258

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=-0.73).
• BP6: Variant 8-101493561-C-T is Benign according to our data. Variant chr8-101493561-C-T is described in ClinVar as [Benign]. Clinvar id is 1253285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.20+772C>T		intron_variant		ENST00000646743.1
GRHL2	NM_001330593.2	c.-29+712C>T		intron_variant
GRHL2	XM_011517306.4	c.-29+975C>T		intron_variant
GRHL2	XM_011517307.4	c.20+772C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+772C>T		intron_variant			NM_024915.4	P1
GRHL2	ENST00000472106.2	n.348+772C>T		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-29+712C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3774 AN: 152098 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0249 AC: 3786 AN: 152206 Hom.: 78 Cov.: 33 AF XY: 0.0236 AC XY: 1754 AN XY: 74410

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0205 Hom.: 9

Bravo AF: 0.0275

Asia WGS AF: 0.0140 AC: 47 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 23, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	10
Dann	Benign	0.92

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: rs150239237; hg19: chr8-102505789;