rs12669309

Positions:

• chr7-80770854-C-A
• chr7-80770854-C-G
• chr7-80770854-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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]

ACMG classification

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
SEMA3C	NM_006379.5	c.1355-5611G>T		intron_variant		ENST00000265361.8
SEMA3C	NM_001350120.2	c.1409-5611G>T		intron_variant
SEMA3C	NM_001350121.2	c.1181-5611G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1355-5611G>T		intron_variant		1	NM_006379.5	P1
SEMA3C	ENST00000419255.6	c.1355-5611G>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36216 AN: 151998 Hom.: 5129 Cov.: 32

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

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

Other links and lift over

dbSNP: rs12669309; hg19: chr7-80400170;