rs11072566

Positions:

• chr15-76001630-A-G

Variant summary

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

The ENST00000394907.8(NRG4):​c.104+7570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,912 control chromosomes in the GnomAD database, including 16,618 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 0.46 (16618 hom., cov: 31)
• Consequence: NRG4 ENST00000394907.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

Genes affected

NRG4 (HGNC:29862): (neuregulin 4) The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG4	NM_138573.4	c.104+7570T>C		intron_variant		ENST00000394907.8	NP_612640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG4	ENST00000394907.8	c.104+7570T>C		intron_variant		1	NM_138573.4	ENSP00000378367	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69161 AN: 151794 Hom.: 16622 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.455 AC: 69168 AN: 151912 Hom.: 16618 Cov.: 31 AF XY: 0.457 AC XY: 33923 AN XY: 74242

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.488

Alfa AF: 0.459 Hom.: 2610

Bravo AF: 0.452

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.82

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: rs11072566; hg19: chr15-76293971;