rs2454472

chr15-75959507-A-T

Variant summary

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

The NM_138573.4(NRG4):c.251+2321T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 151,960 control chromosomes in the GnomAD database, including 609 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 0.062 (609 hom., cov: 32)
• Consequence: NRG4 NM_138573.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG4	NM_138573.4	c.251+2321T>A		intron_variant		ENST00000394907.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG4	ENST00000394907.8	c.251+2321T>A		intron_variant		1	NM_138573.4	P1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9388 AN: 151848 Hom.: 602 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00923

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0523

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

GnomAD4 genome AF: 0.0620 AC: 9426 AN: 151960 Hom.: 609 Cov.: 32 AF XY: 0.0601 AC XY: 4463 AN XY: 74286

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00923

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0518

Alfa AF: 0.0480 Hom.: 49

Bravo AF: 0.0695

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.1
Dann	Benign	0.43

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: rs2454472; hg19: chr15-76251848;