8-32647818-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001322205.2(NRG1):​c.101C>T​(p.Ala34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 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: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NRG1
NM_001322205.2 missense

Scores

3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a site Breakpoint for translocation to form gamma-heregulin (size 0) in uniprot entity NRG1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.080120355).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NRG1NM_013964.5 linkuse as main transcriptc.502+30933C>T intron_variant ENST00000405005.8 NP_039258.1 Q02297-1Q6PK61

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NRG1ENST00000405005.8 linkuse as main transcriptc.502+30933C>T intron_variant 1 NM_013964.5 ENSP00000384620.2 Q02297-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461842
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Uncertain
1.0
Eigen
Benign
-0.13
Eigen_PC
Benign
0.059
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.96
T
PROVEAN
Benign
-0.35
N
REVEL
Benign
0.043
Sift
Uncertain
0.017
D
Sift4G
Benign
0.15
T
Polyphen
0.010
B
Vest4
0.078
MutPred
0.23
Gain of catalytic residue at A34 (P = 0.0053);
MVP
0.47
ClinPred
0.12
T
GERP RS
5.2

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34918173; hg19: chr8-32505337; API