7-80842219-T-C

Variant names:

• chr7-80842219-T-C
• rs4731861
• NM_006379.5:c.104-13474A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006379.5(SEMA3C):​c.104-13474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,068 control chromosomes in the GnomAD database, including 48,363 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 0.80 (48363 hom., cov: 32)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006379.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	NM_006379.5	MANE Select	c.104-13474A>G		intron	N/A	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.158-13474A>G		intron	N/A	NP_001337049.1
	SEMA3C	NM_001350121.2		c.-71-13474A>G		intron	N/A	NP_001337050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.104-13474A>G		intron	N/A	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.277+5041A>G		intron	N/A	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.221-13474A>G		intron	N/A	ENSP00000623846.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120952 AN: 151950 Hom.: 48316 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.796 AC: 121059 AN: 152068 Hom.: 48363 Cov.: 32 AF XY: 0.800 AC XY: 59437 AN XY: 74316

African (AFR) AF: 0.749 AC: 31069 AN: 41472

American (AMR) AF: 0.806 AC: 12279 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3021 AN: 3472

East Asian (EAS) AF: 0.881 AC: 4541 AN: 5154

South Asian (SAS) AF: 0.889 AC: 4292 AN: 4826

European-Finnish (FIN) AF: 0.847 AC: 8972 AN: 10592

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54221 AN: 67996

Other (OTH) AF: 0.798 AC: 1683 AN: 2110

Alfa AF: 0.801 Hom.: 98950

Bravo AF: 0.792

Asia WGS AF: 0.876 AC: 3042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.38
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: rs4731861; hg19: chr7-80471535;