rs7779029

Positions:

• chr7-80902796-T-C

Variant summary

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

The NM_006379.5(SEMA3C):​c.103+13883A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,134 control chromosomes in the GnomAD database, including 2,681 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 0.14 (2681 hom., cov: 32)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.103+13883A>G		intron_variant		ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.157+13883A>G		intron_variant			NP_001337049.1
SEMA3C	NM_001350121.2	c.-72+3033A>G		intron_variant			NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.103+13883A>G		intron_variant		1	NM_006379.5	ENSP00000265361	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21167 AN: 152016 Hom.: 2655 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21246 AN: 152134 Hom.: 2681 Cov.: 32 AF XY: 0.135 AC XY: 10071 AN XY: 74376

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0796 Hom.: 477

Bravo AF: 0.152

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.37

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: rs7779029; hg19: chr7-80532112;