rs114871790

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-101493463-C-A
• chr8-101493463-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024915.4(GRHL2):​c.20+674C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 143,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000070 (0 hom., cov: 30)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.20+674C>A		intron_variant	Intron 1 of 15	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.-29+614C>A		intron_variant	Intron 1 of 15		NP_001317522.1
GRHL2	XM_011517306.4	c.-29+877C>A		intron_variant	Intron 1 of 15		XP_011515608.1
GRHL2	XM_011517307.4	c.20+674C>A		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>A		intron_variant	Intron 1 of 15		NM_024915.4	ENSP00000495564.1
GRHL2	ENST00000472106.2	n.348+674C>A		intron_variant	Intron 1 of 1	1
GRHL2	ENST00000395927.1	c.-29+614C>A		intron_variant	Intron 1 of 15	2		ENSP00000379260.1

Frequencies

GnomAD3 genomes AF: 0.00000698 AC: 1 AN: 143326 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000698 AC: 1 AN: 143326 Hom.: 0 Cov.: 30 AF XY: 0.0000144 AC XY: 1 AN XY: 69452

Gnomad4 AFR AF: 0.0000252

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.96

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;