1-156177767-C-T

Variant names:

• chr1-156177767-C-T
• rs3738581
• ENST00000872469.1:c.*770C>T

Variant summary

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

The ENST00000872469.1(SEMA4A):​c.*770C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,758 control chromosomes in the GnomAD database, including 18,040 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 0.47 (17970 hom., cov: 30)
  • Exomes 𝑓: 0.38 (70 hom.)
• Consequence: SEMA4A ENST00000872469.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 13 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
• retinitis pigmentosa 35

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy 10

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000872469.1. 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_022367.4	MANE Select	c.*770C>T		downstream_gene	N/A	NP_071762.2
	SEMA4A	NM_001193300.2		c.*770C>T		downstream_gene	N/A	NP_001180229.1	Q9H3S1-1
	SEMA4A	NM_001193301.2		c.*770C>T		downstream_gene	N/A	NP_001180230.1	Q9H3S1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA4A	ENST00000872469.1		c.*770C>T		3_prime_UTR	Exon 16 of 16	ENSP00000542528.1
	SEMA4A	ENST00000920832.1		c.*770C>T		3_prime_UTR	Exon 15 of 15	ENSP00000590891.1
	SEMA4A	ENST00000368285.8	TSL:1 MANE Select	c.*770C>T		downstream_gene	N/A	ENSP00000357268.3	Q9H3S1-1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71188 AN: 151786 Hom.: 17929 Cov.: 30

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.382 AC: 326 AN: 854 Hom.: 70 Cov.: 0 AF XY: 0.397 AC XY: 201 AN XY: 506

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.167 AC: 7 AN: 42

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.424 AC: 39 AN: 92

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.439 AC: 151 AN: 344

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.346 AC: 121 AN: 350

Other (OTH) AF: 0.375 AC: 6 AN: 16

GnomAD4 genome AF: 0.469 AC: 71277 AN: 151904 Hom.: 17970 Cov.: 30 AF XY: 0.464 AC XY: 34413 AN XY: 74210

African (AFR) AF: 0.650 AC: 26924 AN: 41408

American (AMR) AF: 0.403 AC: 6155 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1454 AN: 3466

East Asian (EAS) AF: 0.121 AC: 627 AN: 5174

South Asian (SAS) AF: 0.325 AC: 1560 AN: 4804

European-Finnish (FIN) AF: 0.429 AC: 4521 AN: 10544

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28669 AN: 67942

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.436 Hom.: 40589

Bravo AF: 0.475

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.55
PhyloP100		-0.042
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3738581;

hg19: chr1-156147558;