7-80748832-T-C

Variant names:

• chr7-80748832-T-C
• rs1405743
• NM_006379.5:c.1842+66A>G

Variant summary

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

The NM_006379.5(SEMA3C):​c.1842+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,480,254 control chromosomes in the GnomAD database, including 726,114 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 0.95 (68759 hom., cov: 31)
  • Exomes 𝑓: 0.99 (657355 hom.)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1842+66A>G		intron_variant	Intron 17 of 17	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1896+66A>G		intron_variant	Intron 17 of 17		NP_001337049.1
SEMA3C	NM_001350121.2	c.1668+66A>G		intron_variant	Intron 18 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1842+66A>G		intron_variant	Intron 17 of 17	1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.1842+66A>G		intron_variant	Intron 17 of 17	2		ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143959 AN: 152036 Hom.: 68715 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.972

GnomAD4 exome AF: 0.994 AC: 1320757 AN: 1328100 Hom.: 657355 AF XY: 0.995 AC XY: 653153 AN XY: 656382

African (AFR) AF: 0.802 AC: 23360 AN: 29128

American (AMR) AF: 0.990 AC: 28673 AN: 28964

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 20603 AN: 20700

East Asian (EAS) AF: 1.00 AC: 37096 AN: 37096

South Asian (SAS) AF: 0.999 AC: 68727 AN: 68778

European-Finnish (FIN) AF: 1.00 AC: 49848 AN: 49848

Middle Eastern (MID) AF: 0.995 AC: 5150 AN: 5178

European-Non Finnish (NFE) AF: 1.00 AC: 1033326 AN: 1033766

Other (OTH) AF: 0.988 AC: 53974 AN: 54642

GnomAD4 genome AF: 0.947 AC: 144060 AN: 152154 Hom.: 68759 Cov.: 31 AF XY: 0.949 AC XY: 70598 AN XY: 74378

African (AFR) AF: 0.814 AC: 33746 AN: 41470

American (AMR) AF: 0.985 AC: 15037 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3445 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5154 AN: 5154

South Asian (SAS) AF: 0.999 AC: 4820 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

Middle Eastern (MID) AF: 0.997 AC: 291 AN: 292

European-Non Finnish (NFE) AF: 0.999 AC: 67984 AN: 68034

Other (OTH) AF: 0.972 AC: 2057 AN: 2116

Alfa AF: 0.938 Hom.: 10599

Bravo AF: 0.941

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.015
DANN	Benign	0.33
PhyloP100		-1.1
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: rs1405743; hg19: chr7-80378148;