8-101492313-C-T

Variant names:

• chr8-101492313-C-T
• rs541154
• ENST00000520268.1:n.50+137G>A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NR_186783.1(GRHL2-DT):​n.257-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 188,778 control chromosomes in the GnomAD database, including 88,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71128 hom., cov: 34)
  • Exomes 𝑓: 0.97 (17285 hom.)
• Consequence: GRHL2-DT NR_186783.1 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.184

Genes affected

ENSG00000254024 (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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 8-101492313-C-T is Benign according to our data. Variant chr8-101492313-C-T is described in ClinVar as [Benign]. Clinvar id is 1222504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.-457C>T		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.-457C>T		upstream_gene_variant			NM_024915.4	ENSP00000495564.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146999 AN: 152230 Hom.: 71100 Cov.: 34

Gnomad AFR AF: 0.924

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.973 AC: 35459 AN: 36430 Hom.: 17285 AF XY: 0.973 AC XY: 18357 AN XY: 18874

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.894

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 0.898

Gnomad4 SAS exome AF: 0.960

Gnomad4 FIN exome AF: 0.993

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.983

GnomAD4 genome AF: 0.965 AC: 147082 AN: 152348 Hom.: 71128 Cov.: 34 AF XY: 0.964 AC XY: 71840 AN XY: 74490

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.971

Alfa AF: 0.970 Hom.: 10729

Bravo AF: 0.956

Asia WGS AF: 0.924 AC: 3214 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs541154; hg19: chr8-102504541;