ENST00000652575.1:c.97C>T

Variant names:

• chr8-32647298-C-T
• rs4389886
• NM_001414935.1:c.97C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000652575.1(ENSG00000286131):​c.97C>T​(p.His33Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: ENSG00000286131 ENST00000652575.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.37
• Publications: 0 publications found

Genes affected

LOC128092250 (HGNC:0):

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]

NRG1 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652575.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC128092250	NM_001414935.1	MANE Select	c.97C>T	p.His33Tyr	missense	Exon 1 of 1	NP_001401864.1	A0A494C176
	NRG1	NM_013964.5	MANE Select	c.502+30413C>T		intron	N/A	NP_039258.1	Q02297-1
	NRG1	NM_001322205.2		c.-420C>T		5_prime_UTR	Exon 1 of 9	NP_001309134.1	A0A494C0Q4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286131	ENST00000652575.1	MANE Select	c.97C>T	p.His33Tyr	missense	Exon 1 of 1	ENSP00000498936.1	A0A494C176
	NRG1	ENST00000520502.7	TSL:1	c.-420C>T		5_prime_UTR	Exon 1 of 3	ENSP00000433289.1	Q02297-10
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.502+30413C>T		intron	N/A	ENSP00000384620.2	Q02297-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.89
PhyloP100		4.4
PromoterAI		-0.038	Neutral
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4389886; hg19: chr8-32504817;