chr7-80831009-A-G

Variant names:

• chr7-80831009-A-G
• rs10487878
• NM_006379.5:c.104-2264T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006379.5(SEMA3C):​c.104-2264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 152,218 control chromosomes in the GnomAD database, including 325 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 0.037 (325 hom., cov: 32)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.104-2264T>C		intron_variant	Intron 2 of 17	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.158-2264T>C		intron_variant	Intron 2 of 17		NP_001337049.1
SEMA3C	NM_001350121.2	c.-71-2264T>C		intron_variant	Intron 3 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.104-2264T>C		intron_variant	Intron 2 of 17	1	NM_006379.5	ENSP00000265361.3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5612 AN: 152100 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.00772

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0369 AC: 5616 AN: 152218 Hom.: 325 Cov.: 32 AF XY: 0.0420 AC XY: 3125 AN XY: 74426

African (AFR) AF: 0.00772 AC: 321 AN: 41558

American (AMR) AF: 0.0778 AC: 1188 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5160

South Asian (SAS) AF: 0.122 AC: 587 AN: 4818

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0195 AC: 1323 AN: 67998

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0343 Hom.: 109

Bravo AF: 0.0397

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.69
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10487878; hg19: chr7-80460325;