chr7-80746945-T-C

Position:

• chr7-80746945-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006379.5(SEMA3C):​c.1843-1638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,072 control chromosomes in the GnomAD database, including 64,059 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 0.91 (64059 hom., cov: 31)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1843-1638A>G		intron_variant		ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1897-1638A>G		intron_variant			NP_001337049.1
SEMA3C	NM_001350121.2	c.1669-1638A>G		intron_variant			NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1843-1638A>G		intron_variant		1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.1843-1638A>G		intron_variant		2		ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138537 AN: 151954 Hom.: 64050 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.911 AC: 138594 AN: 152072 Hom.: 64059 Cov.: 31 AF XY: 0.911 AC XY: 67761 AN XY: 74342

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.941

Alfa AF: 0.968 Hom.: 26826

Bravo AF: 0.902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.87

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: rs2886792; hg19: chr7-80376261;