8-101492283-G-A

Variant names:

• chr8-101492283-G-A
• rs541226
• ENST00000690034.1:n.16C>T

Variant summary

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

The NR_186783.1(GRHL2-DT):​n.279C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 171,398 control chromosomes in the GnomAD database, including 81,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.98 (72606 hom., cov: 34)
  • Exomes 𝑓: 0.97 (8961 hom.)
• Consequence: GRHL2-DT NR_186783.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0780

Genes affected

ENSG00000289048 (HGNC:):

GRHL2-DT (HGNC:55466): (GRHL2 divergent transcript)

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=-0.62).
• BP6: Variant 8-101492283-G-A is Benign according to our data. Variant chr8-101492283-G-A is described in ClinVar as [Benign]. Clinvar id is 1278689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.-487G>A		upstream_gene_variant		ENST00000646743.1	NP_079191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.-487G>A		upstream_gene_variant			NM_024915.4	ENSP00000495564.1

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148553 AN: 152238 Hom.: 72569 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.982

GnomAD4 exome AF: 0.969 AC: 18456 AN: 19042 Hom.: 8961 AF XY: 0.968 AC XY: 9651 AN XY: 9972

Gnomad4 AFR exome AF: 0.959

Gnomad4 AMR exome AF: 0.896

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.957

Gnomad4 FIN exome AF: 0.990

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.990

GnomAD4 genome AF: 0.976 AC: 148647 AN: 152356 Hom.: 72606 Cov.: 34 AF XY: 0.974 AC XY: 72575 AN XY: 74494

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.979

Alfa AF: 0.977 Hom.: 12087

Bravo AF: 0.968

Asia WGS AF: 0.927 AC: 3225 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs541226; hg19: chr8-102504511;