7-80842219-T-C

Position:

• chr7-80842219-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3C	NM_006379.5	c.104-13474A>G		intron_variant		ENST00000265361.8
SEMA3C	NM_001350120.2	c.158-13474A>G		intron_variant
SEMA3C	NM_001350121.2	c.-71-13474A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3C	ENST00000265361.8	c.104-13474A>G		intron_variant		1	NM_006379.5	P1

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

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.798

Alfa AF: 0.804 Hom.: 72641

Bravo AF: 0.792

Asia WGS AF: 0.876 AC: 3042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.74

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: rs4731861; hg19: chr7-80471535;