rs3735715

chr8-101667681-G-Achr8-101667681-G-T

Variant summary

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

The NM_024915.4(GRHL2):c.*978G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,320 control chromosomes in the GnomAD database, including 18,772 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 0.45 (18728 hom., cov: 33)
  • Exomes 𝑓: 0.66 (44 hom.)
• Consequence: GRHL2 NM_024915.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHL2	NM_024915.4	c.*978G>A		3_prime_UTR_variant	16/16	ENST00000646743.1
GRHL2	NM_001330593.2	c.*978G>A		3_prime_UTR_variant	16/16
GRHL2	XM_011517306.4	c.*978G>A		3_prime_UTR_variant	16/16
GRHL2	XM_011517307.4	c.1763+3163G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHL2	ENST00000646743.1	c.*978G>A		3_prime_UTR_variant	16/16		NM_024915.4	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68365 AN: 151980 Hom.: 18723 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.658 AC: 146 AN: 222 Hom.: 44 Cov.: 0 AF XY: 0.669 AC XY: 99 AN XY: 148

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.818

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.450 AC: 68380 AN: 152098 Hom.: 18728 Cov.: 33 AF XY: 0.452 AC XY: 33614 AN XY: 74358

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.467

Alfa AF: 0.548 Hom.: 23791

Bravo AF: 0.424

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.66

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: rs3735715; hg19: chr8-102679909;