rs201451670

Variant names:

• chr8-32595960-A-G
• rs201451670
• NM_013964.5:c.233A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-32595960-A-G
• chr8-32595960-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013964.5(NRG1):​c.233A>G​(p.Asn78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRG1 NM_013964.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

Genes affected

NRG1 (HGNC:7997): (neuregulin 1) The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13092655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.233A>G	p.Asn78Ser	missense_variant	Exon 2 of 12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.233A>G	p.Asn78Ser	missense_variant	Exon 2 of 12	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;.;T;.;.;.;.;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.90	.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.31	.;.;.;.;.;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.0	N;N;N;N;.;N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.046	D;T;D;T;.;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T;T;T;T;T
Polyphen		0.15, 0.0040, 0.0070, 0.0080	.;.;B;.;.;.;B;B;B;B
Vest4		0.10, 0.076, 0.069, 0.067, 0.040, 0.050
MutPred		0.30		.;.;.;.;.;Gain of phosphorylation at N78 (P = 0.0405);Gain of phosphorylation at N78 (P = 0.0405);Gain of phosphorylation at N78 (P = 0.0405);Gain of phosphorylation at N78 (P = 0.0405);Gain of phosphorylation at N78 (P = 0.0405);
MVP		0.60
MPC		0.17
ClinPred		0.42	T
GERP RS		3.1
Varity_R		0.034
gMVP		0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201451670; hg19: chr8-32453478;