7-80748859-T-C

Variant names:

• chr7-80748859-T-C
• rs2886793
• NM_006379.5:c.1842+39A>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+39A>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 1,575,270 control chromosomes in the GnomAD database, including 772,989 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 (68739 hom., cov: 31)
  • Exomes 𝑓: 0.99 (704250 hom.)
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1842+39A>G		intron	N/A	NP_006370.1
	SEMA3C	NM_001350120.2		c.1896+39A>G		intron	N/A	NP_001337049.1
	SEMA3C	NM_001350121.2		c.1668+39A>G		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.1842+39A>G		intron	N/A	ENSP00000265361.3
	SEMA3C	ENST00000419255.6	TSL:2	c.1842+39A>G		intron	N/A	ENSP00000411193.2

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143938 AN: 152044 Hom.: 68695 Cov.: 31

Gnomad AFR AF: 0.813

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: 0.971

GnomAD2 exomes AF: 0.985 AC: 218046 AN: 221412 AF XY: 0.989

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.994

GnomAD4 exome AF: 0.994 AC: 1415109 AN: 1423108 Hom.: 704250 Cov.: 26 AF XY: 0.995 AC XY: 702392 AN XY: 705908

African (AFR) AF: 0.804 AC: 25492 AN: 31712

American (AMR) AF: 0.990 AC: 37597 AN: 37960

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 23645 AN: 23752

East Asian (EAS) AF: 1.00 AC: 38974 AN: 38974

South Asian (SAS) AF: 0.999 AC: 79666 AN: 79712

European-Finnish (FIN) AF: 1.00 AC: 52250 AN: 52250

Middle Eastern (MID) AF: 0.994 AC: 5481 AN: 5514

European-Non Finnish (NFE) AF: 1.00 AC: 1093969 AN: 1094458

Other (OTH) AF: 0.987 AC: 58035 AN: 58776

GnomAD4 genome AF: 0.947 AC: 144039 AN: 152162 Hom.: 68739 Cov.: 31 AF XY: 0.949 AC XY: 70579 AN XY: 74378

African (AFR) AF: 0.813 AC: 33742 AN: 41490

American (AMR) AF: 0.985 AC: 15036 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: 4821 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67968 AN: 68022

Other (OTH) AF: 0.972 AC: 2056 AN: 2116

Alfa AF: 0.983 Hom.: 84689

Bravo AF: 0.941

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.36
PhyloP100		-2.7
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: rs2886793; hg19: chr7-80378175;