8-101659184-T-C

Position:

• chr8-101659184-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024915.4(GRHL2):​c.1699-5270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,116 control chromosomes in the GnomAD database, including 4,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4714 hom., cov: 32)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.1699-5270T>C		intron_variant		ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.1651-5270T>C		intron_variant			NP_001317522.1
GRHL2	XM_011517306.4	c.1651-5270T>C		intron_variant			XP_011515608.1
GRHL2	XM_011517307.4	c.1699-5270T>C		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.1699-5270T>C		intron_variant			NM_024915.4	ENSP00000495564	P1
GRHL2	ENST00000395927.1	c.1651-5270T>C		intron_variant		2		ENSP00000379260
GRHL2	ENST00000474338.1	n.341-5270T>C		intron_variant, non_coding_transcript_variant		3
GRHL2	ENST00000517674.5	n.268-5270T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37061 AN: 151998 Hom.: 4713 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.244 AC: 37083 AN: 152116 Hom.: 4714 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74374

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.228

Alfa AF: 0.156 Hom.: 390

Bravo AF: 0.249

Asia WGS AF: 0.266 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4734037; hg19: chr8-102671412;