rs1949971

Variant names:

• chr7-80745026-A-G
• rs1949971
• NM_006379.5:c.2124T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-80745026-A-G
• chr7-80745026-A-C
• chr7-80745026-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_006379.5(SEMA3C):​c.2124T>C​(p.Tyr708Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,614,054 control chromosomes in the GnomAD database, including 777,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.93 (66717 hom., cov: 32)
  • Exomes 𝑓: 0.99 (711076 hom.)
• Consequence: SEMA3C NM_006379.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.77
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-80745026-A-G is Benign according to our data. Variant chr7-80745026-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060435.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	NM_006379.5	MANE Select	c.2124T>C	p.Tyr708Tyr	synonymous	Exon 18 of 18	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.2178T>C	p.Tyr726Tyr	synonymous	Exon 18 of 18	NP_001337049.1
	SEMA3C	NM_001350121.2		c.1950T>C	p.Tyr650Tyr	synonymous	Exon 19 of 19	NP_001337050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.2124T>C	p.Tyr708Tyr	synonymous	Exon 18 of 18	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.2298T>C	p.Tyr766Tyr	synonymous	Exon 20 of 20	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.2241T>C	p.Tyr747Tyr	synonymous	Exon 19 of 19	ENSP00000623846.1

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141627 AN: 152114 Hom.: 66682 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.956

GnomAD2 exomes AF: 0.973 AC: 244449 AN: 251216 AF XY: 0.975

Gnomad AFR exome AF: 0.776

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.975

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.996

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.986 AC: 1440790 AN: 1461824 Hom.: 711076 Cov.: 68 AF XY: 0.985 AC XY: 716474 AN XY: 727216

African (AFR) AF: 0.768 AC: 25704 AN: 33466

American (AMR) AF: 0.983 AC: 43968 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 25424 AN: 26132

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39698

South Asian (SAS) AF: 0.959 AC: 82762 AN: 86258

European-Finnish (FIN) AF: 0.997 AC: 53236 AN: 53420

Middle Eastern (MID) AF: 0.948 AC: 5467 AN: 5768

European-Non Finnish (NFE) AF: 0.994 AC: 1105655 AN: 1111978

Other (OTH) AF: 0.975 AC: 58876 AN: 60396

GnomAD4 genome AF: 0.931 AC: 141718 AN: 152230 Hom.: 66717 Cov.: 32 AF XY: 0.932 AC XY: 69399 AN XY: 74438

African (AFR) AF: 0.777 AC: 32258 AN: 41490

American (AMR) AF: 0.976 AC: 14929 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3366 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.951 AC: 4586 AN: 4820

European-Finnish (FIN) AF: 0.997 AC: 10592 AN: 10626

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67598 AN: 68036

Other (OTH) AF: 0.956 AC: 2023 AN: 2116

Alfa AF: 0.961 Hom.: 39095

Bravo AF: 0.925

Asia WGS AF: 0.970 AC: 3372 AN: 3478

EpiCase AF: 0.991

EpiControl AF: 0.991

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.0
DANN	Benign	0.48
PhyloP100		2.8
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: rs1949971; hg19: chr7-80374342; COSMIC: COSV108090206;