rs11979430

Variant names:

• chr7-80879940-C-T
• rs11979430
• NM_006379.5:c.103+36739G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	NM_006379.5	MANE Select	c.103+36739G>A		intron	N/A	NP_006370.1
	SEMA3C	NM_001350120.2		c.157+36739G>A		intron	N/A	NP_001337049.1
	SEMA3C	NM_001350121.2		c.-72+25889G>A		intron	N/A	NP_001337050.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.103+36739G>A		intron	N/A	ENSP00000265361.3
	SEMA3C	ENST00000419255.6	TSL:2	c.103+36739G>A		intron	N/A	ENSP00000411193.2
	SEMA3C	ENST00000411788.5	TSL:5	n.191+25889G>A		intron	N/A	ENSP00000395398.1

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

African (AFR) AF: 0.261 AC: 10826 AN: 41448

American (AMR) AF: 0.0764 AC: 1168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3466

East Asian (EAS) AF: 0.159 AC: 816 AN: 5146

South Asian (SAS) AF: 0.109 AC: 523 AN: 4818

European-Finnish (FIN) AF: 0.0142 AC: 151 AN: 10608

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0528 AC: 3588 AN: 67994

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.0837 Hom.: 1786

Bravo AF: 0.127

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0020
DANN	Benign	0.69
PhyloP100		-4.0
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: rs11979430; hg19: chr7-80509256;