rs11979430

Positions:

• chr7-80879940-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.103+36739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,074 control chromosomes in the GnomAD database, including 1,735 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 0.12 (1735 hom., cov: 32)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.103+36739G>A		intron_variant		ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.157+36739G>A		intron_variant			NP_001337049.1
SEMA3C	NM_001350121.2	c.-72+25889G>A		intron_variant			NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.103+36739G>A		intron_variant		1	NM_006379.5	ENSP00000265361	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17721 AN: 151960 Hom.: 1716 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.117 AC: 17787 AN: 152074 Hom.: 1735 Cov.: 32 AF XY: 0.113 AC XY: 8433 AN XY: 74340

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0812 Hom.: 274

Bravo AF: 0.127

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0020
DANN	Benign	0.69

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: rs11979430; hg19: chr7-80509256;