rs2454472

Variant names:

• chr15-75959507-A-T
• rs2454472
• NM_138573.4:c.251+2321T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG4	NM_138573.4	MANE Select	c.251+2321T>A		intron	N/A	NP_612640.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG4	ENST00000394907.8	TSL:1 MANE Select	c.251+2321T>A		intron	N/A	ENSP00000378367.3
	NRG4	ENST00000461391.5	TSL:1	n.*322+2321T>A		intron	N/A	ENSP00000431810.1
	NRG4	ENST00000568073.5	TSL:1	n.*236+2321T>A		intron	N/A	ENSP00000456778.1

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

African (AFR) AF: 0.171 AC: 7087 AN: 41424

American (AMR) AF: 0.0283 AC: 432 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4818

European-Finnish (FIN) AF: 0.00923 AC: 97 AN: 10508

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0241 AC: 1638 AN: 67978

Other (OTH) AF: 0.0518 AC: 109 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.43
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2454472; hg19: chr15-76251848;