rs12669309

Variant names:

• chr7-80770854-C-A
• rs12669309
• NM_006379.5:c.1355-5611G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-80770854-C-A
• chr7-80770854-C-G
• chr7-80770854-C-T

Variant summary

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

The NM_006379.5(SEMA3C):​c.1355-5611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,118 control chromosomes in the GnomAD database, including 5,145 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 0.24 (5145 hom., cov: 32)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1355-5611G>T		intron_variant	Intron 12 of 17	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1409-5611G>T		intron_variant	Intron 12 of 17		NP_001337049.1
SEMA3C	NM_001350121.2	c.1181-5611G>T		intron_variant	Intron 13 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1355-5611G>T		intron_variant	Intron 12 of 17	1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.1355-5611G>T		intron_variant	Intron 12 of 17	2		ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36216 AN: 151998 Hom.: 5129 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.239 AC: 36286 AN: 152118 Hom.: 5145 Cov.: 32 AF XY: 0.239 AC XY: 17798 AN XY: 74366

African (AFR) AF: 0.386 AC: 16029 AN: 41480

American (AMR) AF: 0.220 AC: 3367 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2084 AN: 5154

South Asian (SAS) AF: 0.253 AC: 1220 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10594

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10665 AN: 67992

Other (OTH) AF: 0.227 AC: 479 AN: 2112

Alfa AF: 0.207 Hom.: 1373

Bravo AF: 0.248

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.080
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: rs12669309; hg19: chr7-80400170;