1-156153439-C-G

Variant names:

• chr1-156153439-C-G
• rs3738582
• ENST00000355014.6:c.-29-1111C>G

Variant summary

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

The NM_001193300.2(SEMA4A):​c.-254-92C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,122 control chromosomes in the GnomAD database, including 5,834 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 0.26 (5832 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: SEMA4A NM_001193300.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 3 publications found

Genes affected

SEMA4A (HGNC:10729): (semaphorin 4A) This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

SEMA4A Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial colorectal cancer type X

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cone-rod dystrophy 10

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 35

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193300.2. 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
	SEMA4A	NM_001193300.2		c.-254-92C>G		intron	N/A	NP_001180229.1	Q9H3S1-1
	SEMA4A	NM_001193301.2		c.-29-1111C>G		intron	N/A	NP_001180230.1	Q9H3S1-1
	SEMA4A	NM_001370568.1		c.-158-2975C>G		intron	N/A	NP_001357497.1	B4DKS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4A	ENST00000355014.6	TSL:1	c.-29-1111C>G		intron	N/A	ENSP00000347117.2	Q9H3S1-1
	SEMA4A	ENST00000920834.1		c.-67C>G		5_prime_UTR	Exon 2 of 16	ENSP00000590893.1
	SEMA4A	ENST00000920835.1		c.-67C>G		5_prime_UTR	Exon 2 of 16	ENSP00000590894.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39457 AN: 151950 Hom.: 5806 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.222 AC: 12 AN: 54 Hom.: 2 Cov.: 0 AF XY: 0.192 AC XY: 5 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 7 AN: 28

Other (OTH) AF: 0.313 AC: 5 AN: 16

GnomAD4 genome AF: 0.260 AC: 39534 AN: 152068 Hom.: 5832 Cov.: 32 AF XY: 0.258 AC XY: 19183 AN XY: 74350

African (AFR) AF: 0.383 AC: 15882 AN: 41438

American (AMR) AF: 0.206 AC: 3154 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3472

East Asian (EAS) AF: 0.356 AC: 1838 AN: 5168

South Asian (SAS) AF: 0.360 AC: 1733 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1307 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13682 AN: 67986

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.102 Hom.: 139

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.042
PromoterAI		0.019	Neutral
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: rs3738582; hg19: chr1-156123230; COSMIC: COSV61773875; COSMIC: COSV61773875;