chr7-80770854-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006379.5(SEMA3C):​c.1355-5611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,118 control chromosomes in the GnomAD database, including 5,145 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 0.24 ( 5145 hom., cov: 32)

Consequence

SEMA3C
NM_006379.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800
Variant links:
Genes affected
SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA3CNM_006379.5 linkuse as main transcriptc.1355-5611G>T intron_variant ENST00000265361.8
SEMA3CNM_001350120.2 linkuse as main transcriptc.1409-5611G>T intron_variant
SEMA3CNM_001350121.2 linkuse as main transcriptc.1181-5611G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA3CENST00000265361.8 linkuse as main transcriptc.1355-5611G>T intron_variant 1 NM_006379.5 P1Q99985-1
SEMA3CENST00000419255.6 linkuse as main transcriptc.1355-5611G>T intron_variant 2 P1Q99985-1

Frequencies

GnomAD3 genomes
AF:
0.238
AC:
36216
AN:
151998
Hom.:
5129
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.386
Gnomad AMI
AF:
0.217
Gnomad AMR
AF:
0.220
Gnomad ASJ
AF:
0.132
Gnomad EAS
AF:
0.404
Gnomad SAS
AF:
0.252
Gnomad FIN
AF:
0.165
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.157
Gnomad OTH
AF:
0.228
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.239
AC:
36286
AN:
152118
Hom.:
5145
Cov.:
32
AF XY:
0.239
AC XY:
17798
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.386
Gnomad4 AMR
AF:
0.220
Gnomad4 ASJ
AF:
0.132
Gnomad4 EAS
AF:
0.404
Gnomad4 SAS
AF:
0.253
Gnomad4 FIN
AF:
0.165
Gnomad4 NFE
AF:
0.157
Gnomad4 OTH
AF:
0.227
Alfa
AF:
0.201
Hom.:
697
Bravo
AF:
0.248
Asia WGS
AF:
0.311
AC:
1084
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.2
DANN
Benign
0.50

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

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

Other links and lift over

dbSNP: rs12669309; hg19: chr7-80400170; API