chr8-101493463-C-G

Variant names:

• chr8-101493463-C-G
• rs114871790
• NM_024915.4:c.20+674C>G

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+674C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 143,386 control chromosomes in the GnomAD database, including 2,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (2390 hom., cov: 30)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0560

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=-0.53).
• BP6: Variant 8-101493463-C-G is Benign according to our data. Variant chr8-101493463-C-G is described in ClinVar as [Benign]. Clinvar id is 1291945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.20+674C>G		intron_variant	Intron 1 of 15	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.-29+614C>G		intron_variant	Intron 1 of 15		NP_001317522.1
GRHL2	XM_011517306.4	c.-29+877C>G		intron_variant	Intron 1 of 15		XP_011515608.1
GRHL2	XM_011517307.4	c.20+674C>G		intron_variant	Intron 1 of 15		XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+674C>G		intron_variant	Intron 1 of 15		NM_024915.4	ENSP00000495564.1
GRHL2	ENST00000472106.2	n.348+674C>G		intron_variant	Intron 1 of 1	1
GRHL2	ENST00000395927.1	c.-29+614C>G		intron_variant	Intron 1 of 15	2		ENSP00000379260.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 20700 AN: 143268 Hom.: 2377 Cov.: 30

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.00484

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.145 AC: 20750 AN: 143386 Hom.: 2390 Cov.: 30 AF XY: 0.147 AC XY: 10217 AN XY: 69546

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0971 Hom.: 173

Bravo AF: 0.148

Asia WGS AF: 0.180 AC: 621 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

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	-0.53
CADD	Benign	15
DANN	Benign	0.89

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: rs114871790; hg19: chr8-102505691;